protein folding

Summary

Summary: A rapid biochemical reaction involved in the formation of proteins. It begins even before a protein has been completely synthesized and proceeds through discrete intermediates (primary, secondary, and tertiary structures) before the final structure (quaternary structure) is developed.

Top Publications

  1. ncbi GROMACS: fast, flexible, and free
    David van der Spoel
    Department of Cell and Molecular Biology, Uppsala University, Husargatan 3, Box 596, S 75124 Uppsala, Sweden
    J Comput Chem 26:1701-18. 2005
  2. ncbi Signal integration in the endoplasmic reticulum unfolded protein response
    David Ron
    The Kimmel Center for Biology and Medicine at the Skirball Institute, New York University School of Medicine, 540 First Avenue, New York, New York 10016, USA
    Nat Rev Mol Cell Biol 8:519-29. 2007
  3. ncbi Protein secondary structure prediction based on position-specific scoring matrices
    D T Jones
    Department of Biological Sciences, University of Warwick, Coventry, CV4 7AL, United Kingdom
    J Mol Biol 292:195-202. 1999
  4. ncbi Protein misfolding, functional amyloid, and human disease
    Fabrizio Chiti
    Dipartimento di Scienze Biochimiche, Universita degli Studi di Firenze, I 50134 Firenze, Italy
    Annu Rev Biochem 75:333-66. 2006
  5. ncbi Molecular chaperones in protein folding and proteostasis
    F Ulrich Hartl
    Department of Cellular Biochemistry, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany
    Nature 475:324-32. 2011
  6. ncbi Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid beta-peptide
    Christian Haass
    Adolf Butenandt Institute, Department of Biochemistry, Laboratory for Alzheimer s and Parkinson s Disease Research, Ludwig Maximilians University, 80336 Munich, Germany
    Nat Rev Mol Cell Biol 8:101-12. 2007
  7. pmc TM-align: a protein structure alignment algorithm based on the TM-score
    Yang Zhang
    Center of Excellence in Bioinformatics, University at Buffalo 901 Washington Street, Buffalo, NY 14203, USA
    Nucleic Acids Res 33:2302-9. 2005
  8. ncbi XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor
    H Yoshida
    Graduate School of Biostudies, Kyoto University, Kyoto 606 8304, Japan
    Cell 107:881-91. 2001
  9. ncbi Crystal structure of the nucleosome core particle at 2.8 A resolution
    K Luger
    Institut fur Molekularbiologie und Biophysik, Zurich, Switzerland
    Nature 389:251-60. 1997
  10. ncbi IUPred: web server for the prediction of intrinsically unstructured regions of proteins based on estimated energy content
    Zsuzsanna Dosztanyi
    Institute of Enzymology, BRC, Hungarian Academy of Sciences, PO Box 7, H 1518 Budapest, Hungary
    Bioinformatics 21:3433-4. 2005

Research Grants

Detail Information

Publications298 found, 100 shown here

  1. ncbi GROMACS: fast, flexible, and free
    David van der Spoel
    Department of Cell and Molecular Biology, Uppsala University, Husargatan 3, Box 596, S 75124 Uppsala, Sweden
    J Comput Chem 26:1701-18. 2005
    ..It is maintained by a group of developers from the Universities of Groningen, Uppsala, and Stockholm, and the Max Planck Institute for Polymer Research in Mainz. Its Web site is http://www.gromacs.org...
  2. ncbi Signal integration in the endoplasmic reticulum unfolded protein response
    David Ron
    The Kimmel Center for Biology and Medicine at the Skirball Institute, New York University School of Medicine, 540 First Avenue, New York, New York 10016, USA
    Nat Rev Mol Cell Biol 8:519-29. 2007
    ..The arms of the UPR are integrated to provide a response that remodels the secretory apparatus and aligns cellular physiology to the demands imposed by ER stress...
  3. ncbi Protein secondary structure prediction based on position-specific scoring matrices
    D T Jones
    Department of Biological Sciences, University of Warwick, Coventry, CV4 7AL, United Kingdom
    J Mol Biol 292:195-202. 1999
    ..Given the success of the method in CASP3, it is reasonable to be confident that the evaluation presented here gives a fair indication of the performance of the method in general...
  4. ncbi Protein misfolding, functional amyloid, and human disease
    Fabrizio Chiti
    Dipartimento di Scienze Biochimiche, Universita degli Studi di Firenze, I 50134 Firenze, Italy
    Annu Rev Biochem 75:333-66. 2006
    ....
  5. ncbi Molecular chaperones in protein folding and proteostasis
    F Ulrich Hartl
    Department of Cellular Biochemistry, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany
    Nature 475:324-32. 2011
    ..Interventions in these and numerous other pathological states may spring from a detailed understanding of the pathways underlying proteome maintenance...
  6. ncbi Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid beta-peptide
    Christian Haass
    Adolf Butenandt Institute, Department of Biochemistry, Laboratory for Alzheimer s and Parkinson s Disease Research, Ludwig Maximilians University, 80336 Munich, Germany
    Nat Rev Mol Cell Biol 8:101-12. 2007
    ..Findings in other neurodegenerative diseases indicate that a broadly similar process of neuronal dysfunction is induced by diffusible oligomers of misfolded proteins...
  7. pmc TM-align: a protein structure alignment algorithm based on the TM-score
    Yang Zhang
    Center of Excellence in Bioinformatics, University at Buffalo 901 Washington Street, Buffalo, NY 14203, USA
    Nucleic Acids Res 33:2302-9. 2005
    ..This correlation could be used to assist in model selection in blind protein structure predictions. The TM-align program is freely downloadable at http://bioinformatics.buffalo.edu/TM-align...
  8. ncbi XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor
    H Yoshida
    Graduate School of Biostudies, Kyoto University, Kyoto 606 8304, Japan
    Cell 107:881-91. 2001
    ..Our results reveal features of the UPR conserved during evolution and clarify the relationship between IRE1- and ATF6-dependent pathways...
  9. ncbi Crystal structure of the nucleosome core particle at 2.8 A resolution
    K Luger
    Institut fur Molekularbiologie und Biophysik, Zurich, Switzerland
    Nature 389:251-60. 1997
    ..The lack of uniformity between multiple histone/DNA-binding sites causes the DNA to deviate from ideal superhelix geometry...
  10. ncbi IUPred: web server for the prediction of intrinsically unstructured regions of proteins based on estimated energy content
    Zsuzsanna Dosztanyi
    Institute of Enzymology, BRC, Hungarian Academy of Sciences, PO Box 7, H 1518 Budapest, Hungary
    Bioinformatics 21:3433-4. 2005
    ..Optional to the prediction are built-in parameter sets optimized for predicting short or long disordered regions and structured domains...
  11. ncbi Molecular chaperones in the cytosol: from nascent chain to folded protein
    F Ulrich Hartl
    Department of Cellular Biochemistry, Max Planck Institut fur Biochemie, Am Klopferspitz 18a, D 82152 Martinsried, Germany
    Science 295:1852-8. 2002
    ..Understanding how the thousands of different proteins synthesized in a cell use this chaperone machinery has profound implications for biotechnology and medicine...
  12. ncbi A "silent" polymorphism in the MDR1 gene changes substrate specificity
    Chava Kimchi-Sarfaty
    Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA
    Science 315:525-8. 2007
    ....
  13. pmc Mistranslation-induced protein misfolding as a dominant constraint on coding-sequence evolution
    D Allan Drummond
    FAS Center for Systems Biology, Harvard University, Cambridge, MA 02138, USA
    Cell 134:341-52. 2008
    ....
  14. ncbi The mammalian unfolded protein response
    Martin Schroder
    School of Biological and Biomedical Sciences, University of Durham, Durham DH1 3LE, United Kingdom
    Annu Rev Biochem 74:739-89. 2005
    ..When protein folding in the ER is inhibited, signal transduction pathways, which increase the biosynthetic capacity and decrease ..
  15. ncbi Protein folding and misfolding
    Christopher M Dobson
    University of Cambridge, Department of Chemistry, Lensfield Road, Cambridge CB2 1EW, UK
    Nature 426:884-90. 2003
    ..Aggregation of misfolded proteins that escape the cellular quality-control mechanisms is a common feature of a wide range of highly debilitating and increasingly prevalent diseases...
  16. pmc Statistical potential for assessment and prediction of protein structures
    Min Yi Shen
    Department of Biopharmaceutical Sciences, Department of Pharmaceutical Chemistry, University of California at San Francisco, San Francisco, California 94158, USA
    Protein Sci 15:2507-24. 2006
    ....
  17. ncbi Regulated translation initiation controls stress-induced gene expression in mammalian cells
    H P Harding
    Skirball Institute of Biomolecular Medicine The Department of Medicine, Kaplan Cancer Center New York University School of Medicine, New York, NY 10016, USA
    Mol Cell 6:1099-108. 2000
    ..Mammalian cells thus utilize an ancient pathway to regulate gene expression in response to diverse stress signals...
  18. pmc Hsp70 chaperones: cellular functions and molecular mechanism
    M P Mayer
    Zentrum für Molekulare Biologie ZMBH, Universitat Heidelberg, Im Neuenheimer Feld 282, 69120, Heidelberg, Germany
    Cell Mol Life Sci 62:670-84. 2005
    ..They assist a large variety of protein folding processes in the cell by transient association of their substrate binding domain with short hydrophobic ..
  19. ncbi Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase
    H P Harding
    Skirball Institute of Biomolecular Medicine, Department of Medicine, NYU School of Medicine, New York 10016, USA
    Nature 397:271-4. 1999
    ..These properties implicate PERK in a signalling pathway that attenuates protein translation in response to ER stress...
  20. pmc XBP-1 regulates a subset of endoplasmic reticulum resident chaperone genes in the unfolded protein response
    Ann Hwee Lee
    Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts 02115, USA
    Mol Cell Biol 23:7448-59. 2003
    ..Collectively, these results suggest that the IRE1/XBP-1 pathway is required for efficient protein folding, maturation, and degradation in the ER and imply the existence of subsets of UPR target genes as defined by ..
  21. ncbi IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA
    Marcella Calfon
    Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA
    Nature 415:92-6. 2002
    ..Our findings suggest that physiological ER load regulates a developmental decision in higher eukaryotes...
  22. ncbi Predicting changes in the stability of proteins and protein complexes: a study of more than 1000 mutations
    Raphael Guerois
    EMBL, Meyerhofstrasse 1, 69117 Heidelberg, Germany
    J Mol Biol 320:369-87. 2002
    ..FOLDEF is available via a web-interface at http://fold-x.embl-heidelberg.de..
  23. pmc The FoldX web server: an online force field
    Joost Schymkowitz
    Switch Laboratory, Flanders Interuniversity Institute for Biotechnology VIB, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussel, Belgium
    Nucleic Acids Res 33:W382-8. 2005
    ..This core functionality will be further extended as more FoldX applications are developed...
  24. ncbi A general model of prion strains and their pathogenicity
    John Collinge
    MRC Prion Unit, Department of Neurodegenerative Disease, UCL Institute of Neurology, London WC1N 3BG, UK
    Science 318:930-6. 2007
    ..Recent advances suggest that prions themselves are not directly neurotoxic, but rather their propagation involves production of toxic species, which may be uncoupled from infectivity...
  25. pmc Generating a prion with bacterially expressed recombinant prion protein
    Fei Wang
    Department of Molecular and Cellular Biochemistry, Ohio State University, Columbus, OH 43210, USA
    Science 327:1132-5. 2010
    ..Thus, as postulated by the prion hypothesis, the infectivity in mammalian prion disease results from an altered conformation of PrP...
  26. ncbi Converging concepts of protein folding in vitro and in vivo
    F Ulrich Hartl
    Max Planck Institute of Biochemistry, Department of Cellular Biochemistry, Martinsried, Germany
    Nat Struct Mol Biol 16:574-81. 2009
    ..Here we review recent concepts emerging from studies of protein folding in vitro and in vivo, with a focus on how proteins navigate the complex folding energy landscape inside cells ..
  27. pmc The HSP70 chaperone machinery: J proteins as drivers of functional specificity
    Harm H Kampinga
    Department of Cell Biology, University of Groningen, University Medical Center, 713 AV Groningen, The Netherlands
    Nat Rev Mol Cell Biol 11:579-92. 2010
    ..Some target HSP70 activity to clients at precise locations in cells and others bind client proteins directly, thereby delivering specific clients to HSP70 and directly determining their fate...
  28. ncbi Scoring function for automated assessment of protein structure template quality
    Yang Zhang
    Center of Excellence in Bioinformatics, University at Buffalo, Buffalo, New York 14203, USA
    Proteins 57:702-10. 2004
    ..These data suggest that the TM-score is a useful complement to the fully automated assessment of protein structure predictions. The executable program of TM-score is freely downloadable at http://bioinformatics.buffalo.edu/TM-score...
  29. ncbi Molecular chaperone functions in protein folding and proteostasis
    Yujin E Kim
    Department of Cellular Biochemistry, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany
    Annu Rev Biochem 82:323-55. 2013
    The biological functions of proteins are governed by their three-dimensional fold. Protein folding, maintenance of proteome integrity, and protein homeostasis (proteostasis) critically depend on a complex network of molecular chaperones...
  30. ncbi How fast-folding proteins fold
    Kresten Lindorff-Larsen
    D E Shaw Research, New York, NY 10036, USA
    Science 334:517-20. 2011
    ..In most cases, folding follows a single dominant route in which elements of the native structure appear in an order highly correlated with their propensity to form in the unfolded state...
  31. pmc One step at a time: endoplasmic reticulum-associated degradation
    Shruthi S Vembar
    Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA
    Nat Rev Mol Cell Biol 9:944-57. 2008
    b>Protein folding in the endoplasmic reticulum (ER) is monitored by ER quality control (ERQC) mechanisms...
  32. ncbi Dynamic interaction of BiP and ER stress transducers in the unfolded-protein response
    A Bertolotti
    Skirball Institute of Biomolecular Medicine, Departments of Medicine and Cell Biology and the Kaplan Cancer Center, New York University School of Medicine, New York, New York 10016, USA
    Nat Cell Biol 2:326-32. 2000
    ..that reside in the endoplasmic reticulum (ER) and transmit stress signals in response to perturbation of protein folding. Here we show that the lumenal domains of these two proteins are functionally interchangeable in mediating an ..
  33. ncbi Inherent toxicity of aggregates implies a common mechanism for protein misfolding diseases
    Monica Bucciantini
    Dipartimento di Scienze Biochimiche, Viale Morgagni 50, Universita degli Studi di Firenze, 50134 Firenze, Italy
    Nature 416:507-11. 2002
    ..This finding provides added evidence that avoidance of protein aggregation is crucial for the preservation of biological function and suggests common features in the origins of this family of protein deposition diseases...
  34. ncbi The deacetylase HDAC6 regulates aggresome formation and cell viability in response to misfolded protein stress
    Yoshiharu Kawaguchi
    Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA
    Cell 115:727-38. 2003
    ..These findings identify HDAC6 as a crucial player in the cellular management of misfolded protein-induced stress...
  35. pmc How significant is a protein structure similarity with TM-score = 0.5?
    Jinrui Xu
    Department of Medical School, Center for Computational Medicine and Bioinformatics, University of Michigan, 100 Washtenaw Avenue, Ann Arbor, MI 48109, USA
    Bioinformatics 26:889-95. 2010
    ..This article aims to answer two questions: (i) what is the statistical significance of TM-score? (ii) What is the probability of two proteins having the same fold given a specific TM-score?..
  36. pmc Proteotoxic stress and inducible chaperone networks in neurodegenerative disease and aging
    Richard I Morimoto
    Department of Biochemistry, Molecular Biology, and Cell Biology, Rice Institute for Biomedical Research, Northwestern University, Evanston, Illinois 60208, USA
    Genes Dev 22:1427-38. 2008
    ....
  37. ncbi ER stress and the unfolded protein response
    Martin Schroder
    School of Biological and Biomedical Sciences, University of Durham, Durham DH1 3LE, UK
    Mutat Res 569:29-63. 2005
    ..g. Alzheimer's disease. Expression of mutant proteins disrupts protein folding in the endoplasmic reticulum (ER), causes ER stress, and activates a signaling network called the unfolded ..
  38. ncbi Protein degradation and protection against misfolded or damaged proteins
    Alfred L Goldberg
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 426:895-9. 2003
    ..A full understanding of the pathogenesis of the protein-folding diseases will require greater knowledge of how misfolded proteins are recognized and selectively degraded...
  39. ncbi Atomic-level characterization of the structural dynamics of proteins
    David E Shaw
    D E Shaw Research, 120 West 45th Street, New York, NY 10036, USA
    Science 330:341-6. 2010
    ..We examined two fundamental processes in protein dynamics--protein folding and conformational change within the folded state--by means of extremely long all-atom MD simulations ..
  40. pmc IRE1 signaling affects cell fate during the unfolded protein response
    Jonathan H Lin
    Howard Hughes Medical Institute, University of California at San Francisco, San Francisco, CA 94158, USA
    Science 318:944-9. 2007
    ..Key findings from our studies in cell culture were recapitulated in photoreceptors expressing mutant rhodopsin in animal models of retinitis pigmentosa...
  41. ncbi Recognition of errors in three-dimensional structures of proteins
    M J Sippl
    Center for Applied Molecular Engineering, University of Salzburg, Austria
    Proteins 17:355-62. 1993
    ..The techniques are even applicable in cases where only the C alpha trace of a protein conformation is available. The capabilities of the technique are demonstrated using correct and incorrect protein folds...
  42. ncbi Molecular chaperones and protein quality control
    Bernd Bukau
    Zentrum fur Molekulare Biologie, Universitat Heidelberg, 69120 Heidelberg, Germany
    Cell 125:443-51. 2006
    ....
  43. ncbi Perk is essential for translational regulation and cell survival during the unfolded protein response
    H P Harding
    Department of Medicine, The Kaplan Cancer Center, New York University School of Medicine, New York 10016, USA
    Mol Cell 5:897-904. 2000
    ..PERK thus plays a major role in the ability of cells to adapt to ER stress...
  44. ncbi Function and structure of inherently disordered proteins
    A Keith Dunker
    Center for Computational Biology and Bioinformatics, Institute for Intrinsically Disordered Protein Research, Indiana University Schools of Medicine and Informatics, Indianapolis, IN 46202, USA
    Curr Opin Struct Biol 18:756-64. 2008
    ....
  45. ncbi Translational control is required for the unfolded protein response and in vivo glucose homeostasis
    D Scheuner
    Howard Hughes Medical Institute, University of Michigan Medical Center, 48109, Ann Arbor, MI, USA
    Mol Cell 7:1165-76. 2001
    ..The results demonstrate that regulation of translation through eIF2alpha phosphorylation is essential for the ER stress response and in vivo glucose homeostasis...
  46. ncbi ER stress regulation of ATF6 localization by dissociation of BiP/GRP78 binding and unmasking of Golgi localization signals
    Jingshi Shen
    Department of Biological Sciences, Columbia University, New York, NY 10027, USA
    Dev Cell 3:99-111. 2002
    ..These results suggest that BiP retains ATF6 in the ER by inhibiting its GLSs and that dissociation of BiP during ER stress allows ATF6 to be transported to the Golgi...
  47. ncbi ER stress and diseases
    Hiderou Yoshida
    Department of Biophysics, Graduate School of Science, Kyoto University, Japan
    FEBS J 274:630-58. 2007
    ..In this review, I will summarize recent progress in this field. Molecules that regulate the ER stress response would be potential candidates for drug targets in various conformational diseases...
  48. ncbi Structure of an intermediate state in protein folding and aggregation
    Philipp Neudecker
    Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada
    Science 336:362-6. 2012
    ....
  49. ncbi The AAA ATPase Cdc48/p97 and its partners transport proteins from the ER into the cytosol
    Y Ye
    Howard Hughes Medical Institute and Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 414:652-6. 2001
    ..We propose that the Cdc48/p97-Ufd1-Npl4 complex extracts proteins from the ER membrane for cytosolic degradation...
  50. ncbi Hsp104, Hsp70, and Hsp40: a novel chaperone system that rescues previously aggregated proteins
    J R Glover
    Howard Hughes Medical Institute and Department of Molecular Genetics and Cell Biology, The University of Chicago, Illinois 60637, USA
    Cell 94:73-82. 1998
    ..coli. We conclude that Hsp104 has a protein remodeling activity that acts on trapped, aggregated proteins and requires specific interactions with conventional chaperones to promote refolding of the intermediates it produces...
  51. pmc The delicate balance between secreted protein folding and endoplasmic reticulum-associated degradation in human physiology
    Christopher J Guerriero
    Department of Biological Sciences, University of Pittsburgh, A320 Langley Hall, Pittsburgh, PA 15260, USA
    Physiol Rev 92:537-76. 2012
    b>Protein folding is a complex, error-prone process that often results in an irreparable protein by-product. These by-products can be recognized by cellular quality control machineries and targeted for proteasome-dependent degradation...
  52. pmc Orchestrating the unfolded protein response in health and disease
    Randal J Kaufman
    Department of Biological Chemistry, Howard Hughes Medical Institute, University of Michigan Medical Center, Ann Arbor 48109 0650, USA
    J Clin Invest 110:1389-98. 2002
  53. ncbi HSP90 at the hub of protein homeostasis: emerging mechanistic insights
    Mikko Taipale
    Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA
    Nat Rev Mol Cell Biol 11:515-28. 2010
    ..Comprehensive understanding of how HSP90 functions promises not only to provide new avenues for therapeutic intervention, but to shed light on fundamental biological questions...
  54. ncbi Amyloid-like aggregates sequester numerous metastable proteins with essential cellular functions
    Heidi Olzscha
    Department of Cellular Biochemistry, Max Planck Institute of Biochemistry, Martinsried, Germany
    Cell 144:67-78. 2011
    ..We suggest that amyloidogenic aggregation targets a metastable subproteome, thereby causing multifactorial toxicity and, eventually, the collapse of essential cellular functions...
  55. ncbi The pairwise energy content estimated from amino acid composition discriminates between folded and intrinsically unstructured proteins
    Zsuzsanna Dosztanyi
    Institute of Enzymology, Biological Research Center, Hungarian Academy of Sciences, 1518 Budapest, PO Box 7, Hungary
    J Mol Biol 347:827-39. 2005
    ..This application we term IUPred and compare its performance with three generally accepted predictors, PONDR VL3H, DISOPRED2 and GlobPlot on a database of disordered proteins...
  56. pmc The evolutionary consequences of erroneous protein synthesis
    D Allan Drummond
    FAS Center for Systems Biology, Harvard University, 52 Oxford Street, Cambridge, MA 02138, USA
    Nat Rev Genet 10:715-24. 2009
    ..We emphasize major areas in which little is known, such as the failure rates of protein folding, in addition to areas in which technological innovations may enable imminent gains, such as the elucidation ..
  57. ncbi Engineering and characterization of a superfolder green fluorescent protein
    Jean Denis Pédelacq
    Bioscience Division, MS M888, Los Alamos National Laboratory, Los Alamos, New Mexico 87545, USA
    Nat Biotechnol 24:79-88. 2006
    ..X-ray crystallographic structural analyses helped explain the enhanced folding of superfolder GFP relative to folding reporter GFP...
  58. pmc The endoplasmic reticulum and the unfolded protein response
    Jyoti D Malhotra
    Howard Hughes Medical Institute, Department of Biological Chemistry, University of Michigan Medical Center, Ann Arbor, MI 48109, United States
    Semin Cell Dev Biol 18:716-31. 2007
    ..are translocated into the ER lumen in an unfolded state and require protein chaperones and catalysts of protein folding to attain their final appropriate conformation...
  59. pmc DisProt: the Database of Disordered Proteins
    Megan Sickmeier
    Department of Biochemistry and Molecular Biology, Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN 46202, USA
    Nucleic Acids Res 35:D786-93. 2007
    ..In addition to being a unique source of biological information, DisProt opens doors for a plethora of bioinformatics studies. DisProt is openly available at http://www.disprot.org...
  60. pmc Linking folding and binding
    Peter E Wright
    Department of Molecular Biology and Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, United States
    Curr Opin Struct Biol 19:31-8. 2009
    ....
  61. pmc Misfolded proteins partition between two distinct quality control compartments
    Daniel Kaganovich
    Department of Biology and BioX Program, Stanford University, Stanford, California 94305, USA
    Nature 454:1088-95. 2008
    ..Our findings provide a framework for understanding the preferential accumulation of amyloidogenic proteins in inclusions linked to human disease...
  62. pmc Identifying the amylome, proteins capable of forming amyloid-like fibrils
    Lukasz Goldschmidt
    Howard Hughes Medical Institute, University of California, Los Angeles, CA 90095 1570, USA
    Proc Natl Acad Sci U S A 107:3487-92. 2010
    ..The implication is that chaperoning effects have evolved to constrain self-complementary segments from interaction with each other...
  63. pmc Understanding protein non-folding
    Vladimir N Uversky
    Institute for Intrinsically Disordered Protein Research, Center for Computational Biology and Bioinformatics, Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
    Biochim Biophys Acta 1804:1231-64. 2010
    ..about intrinsic disorder? What are the functional advantages of disordered proteins/regions? What is the functional repertoire of these proteins? What are the relationships between intrinsically disordered proteins and human diseases?..
  64. pmc Molecular dynamics and protein function
    M Karplus
    Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA
    Proc Natl Acad Sci U S A 102:6679-85. 2005
    ..In this Perspective we survey two areas, protein folding and enzymatic catalysis, in which simulations have contributed to a general understanding of mechanism...
  65. ncbi Protein quality control in the cytosol and the endoplasmic reticulum: brothers in arms
    Alexander Buchberger
    Department of Biochemistry, Biocenter, University of Wurzburg, Am Hubland, 97074 Wurzburg, Germany
    Mol Cell 40:238-52. 2010
    ....
  66. ncbi Sensitive detection of pathological prion protein by cyclic amplification of protein misfolding
    G P Saborio
    Serono Pharmaceutical Research Institute, Geneva, Switzerland
    Nature 411:810-3. 2001
    ....
  67. ncbi A trip to the ER: coping with stress
    D Thomas Rutkowski
    Howard Hughes Medical Institute and Department of Biological Chemistry, University of Michigan Medical Center, Ann Arbor, MI 48109 0650, USA
    Trends Cell Biol 14:20-8. 2004
    ..The UPR alleviates stress by upregulating protein folding and degradation pathways in the ER and inhibiting protein synthesis...
  68. ncbi Protein aggregation and neurodegenerative disease
    Christopher A Ross
    Division of Neurobiology, Department of Psychiatry, Johns Hopkins University School of Medicine, Ross Research Building, Room 618, 720 Rutland Avenue, Baltimore, Maryland 21205, USA
    Nat Med 10:S10-7. 2004
    ..There is now increased understanding of the pathways involved in protein aggregation, and some recent clues have emerged as to the molecular mechanisms of cellular toxicity. These are leading to approaches toward rational therapeutics...
  69. pmc Mammalian transcription factor ATF6 is synthesized as a transmembrane protein and activated by proteolysis in response to endoplasmic reticulum stress
    K Haze
    HSP Research Institute, Kyoto Research Park, Shimogyo ku, Kyoto 600 8813, Japan
    Mol Biol Cell 10:3787-99. 1999
    The unfolded protein response (UPR) controls the levels of molecular chaperones and enzymes involved in protein folding in the endoplasmic reticulum (ER)...
  70. ncbi A membrane protein complex mediates retro-translocation from the ER lumen into the cytosol
    Yihong Ye
    Howard Hughes Medical Institute and Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA
    Nature 429:841-7. 2004
    ..Derlin-1 interacts with US11, a virally encoded ER protein that specifically targets MHC class I heavy chains for export from the ER, as well as with VIMP, a novel membrane protein that recruits the p97 ATPase and its cofactor...
  71. ncbi Biological and chemical approaches to diseases of proteostasis deficiency
    Evan T Powers
    Departments of Chemistry and Molecular and Experimental Medicine and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Annu Rev Biochem 78:959-91. 2009
    ..the principle that proteostasis is influenced both by an adjustable proteostasis network capacity and protein folding energetics, which together determine the balance between folding efficiency, misfolding, protein degradation, ..
  72. pmc Wild-type and mutant SOD1 share an aberrant conformation and a common pathogenic pathway in ALS
    Daryl A Bosco
    Department of Neurology, University of Massachusetts Medical Center, Worcester, Massachusetts, USA
    Nat Neurosci 13:1396-403. 2010
    ..Our findings suggest that wild-type SOD1 can be pathogenic in SALS and identify an SOD1-dependent pathogenic mechanism common to FALS and SALS...
  73. ncbi Protein folding stress in neurodegenerative diseases: a glimpse into the ER
    Soledad Matus
    Center for Molecular Studies of Cell, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile
    Curr Opin Cell Biol 23:239-52. 2011
    ..protein response (UPR), which aims to reestablish homeostasis in part through regulation of genes involved in protein folding, quality control and degradation pathways...
  74. ncbi Protein dynamism and evolvability
    Nobuhiko Tokuriki
    Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel
    Science 324:203-7. 2009
    ..This dynamic view of protein structure, function, and evolvability is extrapolated to describe hypothetical scenarios for the evolution of the early proteins and future research directions in the area of protein dynamism and evolution...
  75. ncbi Topological and energetic factors: what determines the structural details of the transition state ensemble and "en-route" intermediates for protein folding? An investigation for small globular proteins
    C Clementi
    Department of Physics, University of California at San Diego, La Jolla, CA 92093 0319, USA
    J Mol Biol 298:937-53. 2000
    ..This result clearly indicates that, as long as the protein sequence is sufficiently minimally frustrated, topology plays a central role in determining the folding mechanism...
  76. pmc Hyperthermophilic enzymes: sources, uses, and molecular mechanisms for thermostability
    C Vieille
    Biochemistry Department, Michigan State University, East Lansing, Michigan 48824, USA
    Microbiol Mol Biol Rev 65:1-43. 2001
    ..Finally, current uses and potential applications of thermophilic and hyperthermophilic enzymes as research reagents and as catalysts for industrial processes are described...
  77. ncbi Fast and accurate predictions of protein stability changes upon mutations using statistical potentials and neural networks: PoPMuSiC-2.0
    Yves Dehouck
    Bioinformatique génomique et structurale, Université Libre de Bruxelles Av Fr Roosevelt 50, CP165 61, 1050 Brussels, Belgium
    Bioinformatics 25:2537-43. 2009
    ....
  78. pmc The role of aromaticity, exposed surface, and dipole moment in determining protein aggregation rates
    Gian Gaetano Tartaglia
    Department of Biochemistry, University of Zurich, CH 8057, Zurich, Switzerland
    Protein Sci 13:1939-41. 2004
    ..Furthermore, the results of the parameter-free model correlate well with the aggregation propensities of a set of peptides designed by computer simulations...
  79. ncbi Recombinant protein expression in Escherichia coli
    F Baneyx
    Department of Chemical Engineering University of Washington Box 351750, Seattle, WA 98195, USA
    Curr Opin Biotechnol 10:411-21. 1999
    ..Recent progress in the fundamental understanding of transcription, translation, and protein folding in E...
  80. ncbi Adapting proteostasis for disease intervention
    William E Balch
    Department of Cell Biology and Institute for Childhood and Neglected Diseases, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Science 319:916-9. 2008
    ....
  81. ncbi How to study proteins by circular dichroism
    Sharon M Kelly
    Division of Biochemistry and Molecular Biology, Institute of Biomedical and Life Sciences, Joseph Black Building, University of Glasgow, Glasgow G12 8QQ, Scotland, UK
    Biochim Biophys Acta 1751:119-39. 2005
    ..In this article, we summarise the basis of the CD approach and its application to the study of proteins, and then present clear guidelines on how reliable data can be obtained and analysed...
  82. ncbi The mitochondrial UPR - protecting organelle protein homeostasis
    Cole M Haynes
    Cell Biology Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, Box 390, New York, NY 10065, USA
    J Cell Sci 123:3849-55. 2010
    ..Mitochondria have dedicated molecular chaperones and proteases that promote proper protein folding, complex assembly and quality control...
  83. pmc Oxidative protein folding in eukaryotes: mechanisms and consequences
    Benjamin P Tu
    Howard Hughes Medical Institute, Department of Cellular and Molecular Pharmacology, University of California, San Francisco, 94143, USA
    J Cell Biol 164:341-6. 2004
    The endoplasmic reticulum (ER) provides an environment that is highly optimized for oxidative protein folding. Rather than relying on small molecule oxidants like glutathione, it is now clear that disulfide formation is driven by a ..
  84. ncbi S-nitrosylated protein-disulphide isomerase links protein misfolding to neurodegeneration
    Takashi Uehara
    Center for Neuroscience and Aging, Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, California 92037, USA
    Nature 441:513-7. 2006
    ..Thus, PDI prevents neurotoxicity associated with ER stress and protein misfolding, but NO blocks this protective effect in neurodegenerative disorders through the S-nitrosylation of PDI...
  85. ncbi Two distinct stress signaling pathways converge upon the CHOP promoter during the mammalian unfolded protein response
    Yanjun Ma
    Department of Tumor Cell Biology, St Jude Children s Research Hospital, Memphis, TN 38105 2794, USA
    J Mol Biol 318:1351-65. 2002
    ....
  86. pmc The CATH classification revisited--architectures reviewed and new ways to characterize structural divergence in superfamilies
    Alison L Cuff
    Institute of Structural and Molecular Biology, University College London, London, WC1E 6BT, UK
    Nucleic Acids Res 37:D310-4. 2009
    ..Information on the degree of structural diversity in each superfamily and structural overlaps between superfamilies can now be downloaded from the CATH website...
  87. ncbi The transmembrane kinase Ire1p is a site-specific endonuclease that initiates mRNA splicing in the unfolded protein response
    C Sidrauski
    Department of Biochemistry and Biophysics, University of California, School of Medicine, San Francisco 94143 0448, USA
    Cell 90:1031-9. 1997
    ..The addition of purified tRNA ligase completes splicing; we therefore have reconstituted HAC1 mRNA splicing in vitro from purified components...
  88. ncbi A time-dependent phase shift in the mammalian unfolded protein response
    Hiderou Yoshida
    Graduate School of Biostudies, Kyoto University, Kyoto 606 8304, Japan
    Dev Cell 4:265-71. 2003
    ....
  89. pmc Formation of native prions from minimal components in vitro
    Nathan R Deleault
    Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755, USA
    Proc Natl Acad Sci U S A 104:9741-6. 2007
    ..These results show that prions able to infect wild-type hamsters can be formed from a minimal set of components including native PrP(C) molecules, copurified lipid molecules, and a synthetic polyanion...
  90. pmc IRE1-mediated unconventional mRNA splicing and S2P-mediated ATF6 cleavage merge to regulate XBP1 in signaling the unfolded protein response
    Kyungho Lee
    Howard Hughes Medical Institute, University of Michigan Medical Center, Ann Arbor, Michigan 48109, USA
    Genes Dev 16:452-66. 2002
    ..Both processing of ATF6 and IRE1alpha-mediated splicing of XBP1 mRNA are required for full activation of the UPR...
  91. pmc The unfolded protein response: a pathway that links insulin demand with beta-cell failure and diabetes
    Donalyn Scheuner
    Department of Biological Chemistry, and Howard Hughes Medical Institute, The University of Michigan Medical Center, Ann Arbor, Michigan 48109, USA
    Endocr Rev 29:317-33. 2008
    ..The study of protein folding and trafficking within the ER is an extremely active area of research that has provided novel insights into ..
  92. pmc Prion hypothesis: the end of the controversy?
    Claudio Soto
    Mitchell Center for Alzheimer s Disease and Related Brain Disorders, Department of Neurology, The University of Texas Medical School at Houston, 6431 Fannin St, Houston, TX 77030, USA
    Trends Biochem Sci 36:151-8. 2011
    ..Future research promises to reveal many more intriguing features about the rogue prions...
  93. pmc Comprehensive characterization of genes required for protein folding in the endoplasmic reticulum
    Martin C Jonikas
    Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94143, USA
    Science 323:1693-7. 2009
    b>Protein folding in the endoplasmic reticulum is a complex process whose malfunction is implicated in disease and aging...
  94. ncbi Peripheral protein quality control removes unfolded CFTR from the plasma membrane
    Tsukasa Okiyoneda
    Department of Physiology, and Groupe de Recherche Axé sur la Structure des Protéine GRASP McGill University, Montreal, Quebec H3G 1Y6, Canada
    Science 329:805-10. 2010
    ....
  95. ncbi Decay of endoplasmic reticulum-localized mRNAs during the unfolded protein response
    Julie Hollien
    Department of Cellular and Molecular Pharmacology, University of California San Francisco, Howard Hughes Medical Institute, San Francisco, CA 94143, USA
    Science 313:104-7. 2006
    ..This response is well suited to complement other UPR mechanisms because it could selectively halt production of proteins that challenge the ER and clear the translocation and folding machinery for the subsequent remodeling process...
  96. ncbi Plasma cell differentiation and the unfolded protein response intersect at the transcription factor XBP-1
    Neal N Iwakoshi
    Department of Immunology and Infectious Diseases, Harvard School of Public Health 651 Huntington Avenue, Boston, Massachusetts 02115 6017, USA
    Nat Immunol 4:321-9. 2003
    ..We also show that XBP-1 is involved in controlling the production of interleukin-6, a cytokine that is essential for plasma cell survival. Thus, signals upstream and downstream of XBP-1 integrate plasma cell differentiation with the UPR...
  97. pmc How protein stability and new functions trade off
    Nobuhiko Tokuriki
    Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel
    PLoS Comput Biol 4:e1000002. 2008
    ..Thus, the evolution of new enzymatic activities, both in nature and in the laboratory, is dependent on the compensatory, stabilizing effect of apparently "silent" mutations in regions of the protein that are irrelevant to its function...
  98. pmc Yeast cells provide insight into alpha-synuclein biology and pathobiology
    Tiago Fleming Outeiro
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    Science 302:1772-5. 2003
    ..This readily manipulable system provides an opportunity to dissect the molecular pathways underlying normal alpha-synuclein biology and the pathogenic consequences of its misfolding...
  99. pmc IRE1alpha kinase activation modes control alternate endoribonuclease outputs to determine divergent cell fates
    Dan Han
    Department of Medicine, University of California, San Francisco, San Francisco, CA 94143 2520, USA
    Cell 138:562-75. 2009
    ..We propose that divergent cell fates during ER stress hinge on a balance between IRE1alpha RNase outputs that can be tilted with kinase inhibitors to favor survival...
  100. pmc OS-9 and GRP94 deliver mutant alpha1-antitrypsin to the Hrd1-SEL1L ubiquitin ligase complex for ERAD
    John C Christianson
    Department of Biological Sciences and Bio X Program, Stanford University, Lorry Lokey Bldg, 337 Campus Drive, Stanford, CA 94305, USA
    Nat Cell Biol 10:272-82. 2008
    ..These data suggest that XTP3-B and OS-9 are components of distinct, partially redundant, quality control surveillance pathways that coordinate protein folding with membrane dislocation and ubiquitin conjugation in mammalian cells.
  101. ncbi The complete atomic structure of the large ribosomal subunit at 2.4 A resolution
    N Ban
    Department of Molecular Biophysics and Biochemistry and Howard Hughes Medical Institute, New Haven, CT 06520 8114, USA
    Science 289:905-20. 2000
    ..Most of the proteins stabilize the structure by interacting with several RNA domains, often using idiosyncratically folded extensions that reach into the subunit's interior...

Research Grants77

  1. DnaK Protein Inhibitor Antimicrobials
    Michael Sturgess; Fiscal Year: 2003
    ..Pyrrhocoricin, drosocin and perhaps apidaecin appear to inhibit chaperone-assisted protein folding via binding to the multihelical lid region of the 70 kDa heat shock protein DnaK with their amino terminal ..
  2. NIH Director's Pioneer Award
    Junying Yuan; Fiscal Year: 2009
    ..No Abstract provided ..
  3. H1R Signaling and Immune Deviation in EAE
    Cory Teuscher; Fiscal Year: 2013
    ..This domain is associated with signal transduction, but may also be important in protein folding and trafficking, like the intracellular domains of other G-protein coupled receptors (GPCRs)...
  4. Regulation of ER stress-induced cell death
    Randal J Kaufman; Fiscal Year: 2013
    ..nutrient fluctuations and insulin resistance drive beta cells to synthesize insulin beyond their capacity for protein folding and secretion and activates the unfolded protein response (UPR)...
  5. ER stress: role in myocyte apoptosis and myocardial remodeling
    Krishna Singh; Fiscal Year: 2013
    ..The endoplasmic reticulum (ER or sarcoplasmic reticulum in cardiac myocytes) is a principal site for protein folding, calcium storage and calcium signaling...
  6. A fully validated assay to identify activators of ERSR in human glioma cells: ide
    Maurizio Grimaldi; Fiscal Year: 2012
    ..cells during ERSR produce higher levels of GRP78, the key architect of ERSR and a chaperone involved in protein folding in the ER than astrocytes...
  7. Ferritin: Protein/mRNA/DNA in Fe/O Regulation/Metabolism
    ELIZABETH C contact THEIL; Fiscal Year: 2010
    ..from the ferritin protein cage, as chelated/bound Fe2+ after reduction of the mineral, depend on localized protein folding/unfolding of the cage pores...
  8. MOUSE MODEL FOR DISEASES OF PROTEIN MISFOLDING
    P Michael Conn; Fiscal Year: 2012
    ..designed to develop and characterize two prototypic genetically modified mouse models for human diseases of protein folding. These models are required to bring a novel class of target-specific drugs, pharmacoperones, to human (and ..
  9. Endoplasmic Reticulum Chaperone as a Regulator of Obesity and Diabetes
    Amy S Lee; Fiscal Year: 2010
    ..multifunctional ER chaperone protein GRP78/BiP, is a master regulator of ER homeostasis due to its control of protein folding and the activation of trans-membrane ER stress sensors...
  10. Dietary Cholesterol and Defects in Cholesterol Synthesis
    ROBERT DAVID STEINER; Fiscal Year: 2013
    ..alters the structure, composition and signaling function of plasma membrane caveolae, impairs ER-specific protein folding activity, and causes cellular oxidative stress and apoptosis...
  11. Protein Modifications and Unfolded Protein Response in Diabetic Embryopathy
    Zhiyong Zhao; Fiscal Year: 2013
    ..ER stress activates so-called unfolded protein response (UPR) to resolve protein folding crisis and alter cellular activities...
  12. CSHL 2010 Conference on Molecular Genetics and Bacteria & Phages
    David J Stewart; Fiscal Year: 2010
    ..repair, transposition, transcription, control of gene expression, translation, signaling, heat shock, protein folding and secretion, stress response, cell development and division, and pathogenesis...
  13. SIRT1 as a regulator of health and lifespan of mammals
    David A Sinclair; Fiscal Year: 2013
    ..SIRT1 is the best studied. Major processes controlled by SIRT1 include DNA repair, protein folding, fatty acid and glucose metabolism, hypoxic responses, autophagy, and anti-apoptotic mechanisms...
  14. Genetically testing interactions of ER and oxidative stresses in retinal disease
    Douglas Gould; Fiscal Year: 2013
    ..signaling cascades that seek to restore a homeostasis between the demands of protein production and the protein folding capacity of the ER. Chronic ER stress generates reactive oxygen species that lead to oxidative damage...
  15. 2012 CSHL Bacteria &Phages Conference
    David J Stewart; Fiscal Year: 2012
    ..repair, transposition, transcription, control of gene expression, translation, signaling, heat shock, protein folding and secretion, stress response, cell development and division, and pathogenesis...
  16. Atherogenic mechanism of lipid peroxidation-derived aldehydes
    Sanjay Srivastava; Fiscal Year: 2013
    ..To probe causality, we will examine whether treatment with chemical chaperones, which assist protein folding, would decrease lesion formation and improve plaque stability...
  17. Mechanisms of assembly of photoreceptor G protein complexes
    Barry M Willardson; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Proper protein folding is a key issue in maintaining healthy, functional neurons...
  18. The role fo the TPP1 peotein in telomerase function and cancer cell survival
    Jayakrishnan Nandakumar; Fiscal Year: 2013
    ..As a technician I studied protein folding, then, as a graduate student I employed biochemistry and x-ray crystallography to study RNA/DNA repair, and ..
  19. CFTR Biogenesis and Function in Epithelia
    Zsuzsa Bebok; Fiscal Year: 2012
    ..Thus, a very significant finding in our preliminary studies is that the popular model of protein folding disorders, ?F508 CFTR, also exhibits mRNA structural defects...
  20. Retroviral Subversion of ERAD and Intrinsic Immunity
    JAQUELIN PAGE DUDLEY; Fiscal Year: 2013
    ..signal peptide (SP) to direct translation to the endoplasmic reticulum (ER), where an error-prone process of protein folding and modification occur...
  21. Photocleavable Bead Technology for Glycomics
    Mark Lim; Fiscal Year: 2013
    ..modifications of proteins (PTMs) play a central role in diverse cellular processes including protein folding, targeting, signal transduction, immune response, adherence, motility and protein degradation...
  22. Separation-of-function Mutants to Study the Biological Significance of Telomerase
    Jayakrishnan Nandakumar; Fiscal Year: 2012
    ..As a technician I studied protein folding, then, as a graduate student I employed biochemistry and x-ray crystallography to study RNA/DNA repair, and ..
  23. Defining the role of proteostasis pathways in cancer drug resistance
    ERICA LYNN CAIN; Fiscal Year: 2013
    ..a significant burden on the proteostatic machinery that exists to sense and respond to changes in cellular protein folding requirements...
  24. Identification of key tumor cell-released factors that induce cachexia
    Yi Ping Li; Fiscal Year: 2013
    ..Traditionally, HSPs are primarily known as intracellular molecular chaperones for protein folding, assembly, and translocation, thus making them cytoprotective...
  25. Seahorse XF96 Extracellular Flux Analyzer
    Enrique Saez; Fiscal Year: 2013
    ..function, the Seahorse XF96 Extracellular Flux Analyzer will facilitate and enhance our research on metabolism and metabolic diseases, cancer, neurodegenerative diseases, aging, calorie restriction, and diseases of protein folding.
  26. CELLULAR MECHANISMS OF INHERITED RETINAL DEGENERATION
    Matthew M Lavail; Fiscal Year: 2013
    ..The UPR then upregulates genes that increase the ER's protein folding capacity. If homeostasis cannot be restored, UPR signaling eventually induces cell death by apoptosis...
  27. Heat shock protein 90 antagonist-based therapy of mantle cell lymphoma
    Kapil Bhalla; Fiscal Year: 2012
    ..This strategy involves combinations of treatments with heat shock protein 90 and proteosome inhibitors designed to target protein folding and degradation in MCL cells.
  28. Mitochondrial chaperones mortalin and Tid1 in protein degradation
    Carolyn K Suzuki; Fiscal Year: 2012
    ..proteases, which degrade misfolded and damaged proteins, as well as molecular chaperones, which mediate protein folding and facilitate protein degradation...
  29. Pathogenic Mechanisms of Fatty Liver Disease
    Mohammad S Siddiqui; Fiscal Year: 2011
    ..The ER is an intracellular organelle involved in protein folding, packaging and secretion...
  30. Adiporedoxin, a Novel Player in Adipokine Secretion
    Paul F Pilch; Fiscal Year: 2013
    ..R.) where various chaperones and redox-sensitive enzymes are involved in protein folding and disulfide bond formation. We recently discovered a novel membrane protein of the E.R...
  31. Role of the Unfolded Protein Response in Beta Cell
    Randal J Kaufman; Fiscal Year: 2013
    ..ER, PERK, IREIa, and ATF6a are activated to increase the capacity of the ER to meet the demand for increased protein folding and to increase the protein degradative machinery to eliminate misfolded proteins...
  32. Heat shock proteins in brain ischemia and stroke
    Midori A Yenari; Fiscal Year: 2013
    ..cytoprotective properties by nature of its chaperone functions, presumably leading to enhancement of nascent protein folding and prevention of protein aggregation...
  33. Novel Hsp90 Inhibitors to Reduce Misfolded Proteins in Alzheimer's Disease
    Mary L Michaelis; Fiscal Year: 2011
    ..recent research has been focused on molecular chaperones, the cellular machinery responsible for maintaining protein folding or mediating the degradation of irreparably damaged proteins...
  34. Transgenic Study of ALS-Linked CCS Mutations
    Han Xiang Deng; Fiscal Year: 2011
    ..Biochemical analysis demonstrated that these two ALS- associated CCS mutants exhibit remarkable defects in protein folding/refolding and significantly increased propensity to form fibrillar aggregates...
  35. BIOGENESIS OF MELANOSOMES
    Seth J Orlow; Fiscal Year: 2013
    ..the effects of tyrosinase polymorphisms - such as those associated with vitiligo and melanoma risk - on protein folding and enzyme activity...
  36. Degradation of Endoplasmic Reticulum Chaperones by Chaperone-mediated Autophagy
    Roberta Kiffin; Fiscal Year: 2010
    ..Thus, increased synthesis of these chaperones is one of the first cellular responses to compromised protein folding in the ER, and the mechanisms leading to their upregulation are now well-characterized...
  37. Single Molecule Dynamics of mRNA Translation
    Yale E Goldman; Fiscal Year: 2013
    Regulation of translation rate is of crucial importance for such downstream co-translational pro- cesses as protein folding and modification, ligand binding, oligomerization, and interactions with chaperones and membranes...
  38. A Mouse Model for the Rare Plasma Cell Disease AL Amyloidosis
    David C Seldin; Fiscal Year: 2010
    ..It also has features of a protein folding disorder, in that the pathology in the disease is caused by deposition of the immunoglobulin light chains ..
  39. Drug-like small molecule modulators of the Integrated Stress Response
    David Ron; Fiscal Year: 2010
    ..The protein folding environment in the ER is controlled by a small number of signal transduction pathways and these respond to ER ..
  40. Regulated biosynthesis and function of ABC-transport systems
    Patrick H Thibodeau; Fiscal Year: 2013
    ..The long-term goals of this study are to elucidate how changes in protein folding are manifest within the cell and how these changes are recognized by cellular quality control systems...
  41. Center for Protein Folding Machinery
    Vijay S Pande; Fiscal Year: 2013
    ..and highly interdisciplinary approaches and methodologies to obtain a quantitative understanding of cellular protein folding nanomachines such as mammalian TRiC and the archaeal Mm-cpn chaperonins...
  42. Quantitative analysis of the evolving genotype-to-phenotype map
    DANIEL JAROSZ; Fiscal Year: 2012
    ..Promising insight is emerging from a seemingly distant field - protein folding. To function, proteins must adopt complex, often metastable conformations...
  43. Phase II/III Study of Arimoclomol in the Treatment of SOD1 Positive Familial?.
    Merit E Cudkowicz; Fiscal Year: 2013
    ..Arimoclomol, a co-inducer of heat shock protein gene expression, promotes de novo protein folding, facilitates repair of misfolded proteins and targets misfolded proteins for degradation...
  44. Quantitative analysis of the evolving genotype-to-phenotype map
    DANIEL JAROSZ; Fiscal Year: 2013
    ..Promising insight is emerging from a seemingly distant field - protein folding. To function, proteins must adopt complex, often metastable conformations...
  45. Cytoskeletal Pliability within Cells under Stress: RBCs and Marrow-derived SCs
    Dennis E Discher; Fiscal Year: 2012
    ..We seek to understand directly within intact cells protein folding/unfolding and association, and we have developed an in situ tagging approach for such purposes...
  46. STRUCTURAL BASIS OF ORGANELLE TETHERING
    Adam D Linstedt; Fiscal Year: 2013
    ..that arise from defective protein products in which these proteins depend on secretory processes such as protein folding, quality control, glycosylation, proteolytic activation, and localization...
  47. Endoplasmic reticulum quality control of mutant HexA enzyme in Tay-Sachs disease
    Devin Dersh; Fiscal Year: 2013
    ..allow for the use of drugs that can cross the blood- brain barrier and specifically alter the quality control factors important in the production of HexA without causing global ER stress or affecting general protein folding and ERAD.
  48. Heat Shock Protein Therapeutics for Stroke
    Frank R Sharp; Fiscal Year: 2013
    ..including Hsp70, are chaperones induced by heat shock and many stresses including ischemia and assist protein folding during protein synthesis and re-folding after protein denaturation...
  49. Elucidating Protein Folding Mechanisms
    Jay R Winkler; Fiscal Year: 2010
    b>Protein folding, the final step in the cellular pathway that translates the information stored in a DNA sequence into a heteropolymeric molecule with a structure-defined function, is of such paramount importance for cell survival that ..
  50. Conformational Changes Underlying Intracellular Gating of the Leucine Transporter
    Kelli Kazmier; Fiscal Year: 2012
    ..will be employed to generate the first empirical model of the open-in conformation using the de novo protein folding algorithm Rosetta...
  51. MOLECULAR PATHOLOGY OF VASCULAR INJURY
    Dario C Altieri; Fiscal Year: 2013
    ..of the permeability transition pore, notably Cyclophilin D (CypD), and antagonize its function via a protein folding mechanism that maintains mitochondrial integrity and blocks cell death...
  52. Molecular Mechanisms of Lifespan Extension by Dietary Restriction in Drosophila
    Pankaj Kapahi; Fiscal Year: 2013
    ..upon DR, despite a decrease in global translation which included genes involved in mitochondrial functions, protein folding, fat metabolism and calcium signaling [1]...
  53. Alcohol abuse and Endoplasmic Reticulum dysfunction in exocrine pancreas
    Aurelia Lugea; Fiscal Year: 2013
    ..of this project is to determine the pathologic biochemical events of alcohol abuse that impair ER function, protein folding and transit through the secretory pathway...
  54. Roles of the Unfolded Protein Response in Cell Cycle
    MAHO R NIWA; Fiscal Year: 2013
    ..Demand for increased ER protein folding capacity is sensed by the Unfolded Protein Response signaling pathway (UPR), conserved in all eukaryotes...
  55. Genetic analysis and regulation of amyloids flux in the Drosophila heart
    GIRISH CHANDRA MELKANI; Fiscal Year: 2011
    ..we hypothesize that expression of HD- or AD-causing amyloids in the heart will disrupt the overall balance of protein folding quality control due to oxidative stress or global misfolding, resulting in loss of tissue function...
  56. Membrane Protein Folding and Assembly
    Stephen H White; Fiscal Year: 2013
    ..Our goal is to tighten the connection between the physical and biological principles as a basis for prediction algorithms. ..
  57. Mechanism of CHIP-mediated Ubiquitination of Chaperone-bound Proteins
    Saurav Misra; Fiscal Year: 2012
    Intracellular chaperones not only regulate protein folding but are also key mediators of the degradation and disposal of misfolded and damaged proteins...
  58. Endoplasmic Reticulum Stress in Retinal Degeneration
    Jonathan Lin; Fiscal Year: 2013
    ..To test this hypothesis, we will 1) investigate how UPR signaling regulates rhodopsin protein folding;2) test if we can enhance photoreceptor cell survival in vivo by artificial control of UPR;and 3) determine ..
  59. Co-chaperone role of phosducin-like protein in G protein subunit assembly
    Barry M Willardson; Fiscal Year: 2010
    ..of the Pdc family, PhLP2 and PhLP3, do not bind G beta/gamma, but they have also been implicated in other protein folding processes...
  60. Protein Misfolding Diseases and Oxido-Reductive Pathways
    Ivor J Benjamin; Fiscal Year: 2013
    ..Validation in mice of interacting genes and pathways will provide us target candidates for pharmacolog ..
  61. Protein Misfolding Diseases and Oxido-Reductive Pathways
    Ivor J Benjamin; Fiscal Year: 2011
    ..Validation in mice of interacting genes and pathways will provide us target candidates for pharmacolog ..
  62. REGULATION OF THE HEAT SHOCK RESPONSE IN E. COLI
    CAROL ANNE GROSS; Fiscal Year: 2013
    ..We identified and are dissecting the two homeostatic circuits that monitor protein folding in all compartments of the bacterial cell...
  63. Epithelial-fibroblast Interactions in Lung Fibrosis
    Timothy S Blackwell; Fiscal Year: 2013
    ..Mutant forms of SFTPC impact protein folding in the endoplasmic reticulum (ER), resulting in ER stress...
  64. From Unfolded Proteins in the ER to Disease
    Linda Hendershot; Fiscal Year: 2009
    ..surface or for the external milieu are first translocated into the endoplasmic reticulum (ER) where initial protein folding and modifications occur that are essential for the protein to attain its appropriate functional conformation ..
  65. EXPORT OF PROTEINS IN ESCHERICHIA COLI
    Linda Randall; Fiscal Year: 2002
    ..Strong emphasis is put on understanding the role of protein folding during the process, including both the intrinsic folding properties of the proteins to be exported and the ..
  66. Single Molecule Protein and Biopolymer Folding Dynamics
    Shimon Weiss; Fiscal Year: 2003
    The objective of this proposal is to study protein folding using single-molecule fluorescence methodology. Understanding protein folding is fundamental to deciphering how the genetic code is translated into functional protein units...
  67. Screening for Inhibitors of the Integrated Stress Response
    David Ron; Fiscal Year: 2007
    ..The protein folding environment in the ER is regulated by signal transduction pathways that together constitute the ER unfolded ..
  68. The role of N-glycosylation on beta-sheet protein folding energetics
    JOSHUA L PRICE; Fiscal Year: 2010
    ..suggests that N-glycans (attached to the amide nitrogen of an Asn side-chain) play crucial roles in mediating protein folding and secretion by directly increasing protein folding rates and stability...
  69. Synthesis and Study of Minimal Protein Folding Models: Molecular Torsion Balance
    Craig S Wilcox; Fiscal Year: 2010
    ..in our understanding of the molecular forces that influence biological phenomena (events including protein folding, protein-protein recognition, drug-receptor binding, and enzyme catalysis) require precise observations in ..
  70. Sensing Protein Folding Capacity in the Cell During Aging
    ROCKLAND L WISEMAN; Fiscal Year: 2010
    ..The long-term health of all cells is inextricably linked to protein folding and sustainability of function...
  71. Mannosidase inhibitors as therapeutics for glycoprotein misfolding diseases
    Kelley W Moremen; Fiscal Year: 2010
    ..Many loss-of-function human genetic diseases result from mutations that cause delayed protein folding kinetics rather than generating terminally misfolded polypeptides...
  72. Proteostasis sensors to assess the cellular protein folding capacity
    RICHARD I contact MORIMOTO; Fiscal Year: 2010
    ..These "proteostasis sensors" are designed to provide real-time assessment of the capabilities of protein folding quality control in each compartment of the cell and to assess the consequences of protein damage, cell stress,..
  73. PROTEIN FOLDING &UNFOLDING BY DQC CYTOCHROME C
    Jack H Freed; Fiscal Year: 2011
    ..Cytochrome c is a model system in protein folding studies and it serves as a testing ground for new methods...
  74. Molecular/Chemistry Chaperones and Hemoglobinopathies
    William Welch; Fiscal Year: 2003
    b>Protein folding abnormalities resulting from mutations in the coding regions of many genes represent the molecular basis for a large number of disease states...
  75. Fast Kinetic Studies of Protein Folding and Function
    David Kliger; Fiscal Year: 2007
    ..A major goal is the determination of a parameter that is fundamental to understanding the nature of protein folding: the speed with which the different unfolded conformations interconvert with one another...
  76. PROTEIN FOLDING THERMODYNAMICS AND KINETICS
    Charles Brooks; Fiscal Year: 2005
    The primary objective of this proposed work is the development of fundamental links between the nature of the protein folding free energy landscape and the underlying mechanism and kinetics of protein folding...
  77. MOLECULAR DYNAMICS SIMULATIONS OF PROTEIN UNFOLDING
    Valerie Daggett; Fiscal Year: 1999
    The immediate goal of the proposed research is to perform realistic molecular modeling studies relating to protein folding. Although much is known of the structural details of the native folded conformation of proteins, very little is ..