- Combinatorial patterns of histone acetylations and methylations in the human genome
Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, US National Institutes of Health, Bethesda, Maryland 20892, USA
Nat Genet 40:897-903. 2008
..Our data suggest that these histone modifications may act cooperatively to prepare chromatin for transcriptional activation...
- Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
Nature 447:799-816. 2007
..Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function...
- Crystal structure of the nucleosome core particle at 2.8 A resolution
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...
- Diversity and complexity in DNA recognition by transcription factors
Banting and Best Department of Medical Research, University of Toronto, Toronto, ON M5S 3E1, Canada
Science 324:1720-3. 2009
..This complexity in DNA recognition may be important in gene regulation and in the evolution of transcriptional regulatory networks...
- Genome-wide profiles of STAT1 DNA association using chromatin immunoprecipitation and massively parallel sequencing
British Columbia Cancer Agency Genome Sciences Centre, 675 West 10th Avenue, Vancouver, British Columbia V5Z 4S6, Canada
Nat Methods 4:651-7. 2007
..ChIP-seq targets were enriched in sequences similar to known STAT1 binding motifs. Comparisons with two ChIP-PCR data sets suggested that ChIP-seq sensitivity was between 70% and 92% and specificity was at least 95%...
- Genome-wide mapping of in vivo protein-DNA interactions
David S Johnson
Department of Genetics, Stanford University School of Medicine, Stanford, CA, 94305 5120, USA
Science 316:1497-502. 2007
..96] and statistical confidence (P <10(-4)), properties that were important for inferring new candidate interactions. These include key transcription factors in the gene network that regulates pancreatic islet cell development...
- Robust hepatitis C virus infection in vitro
Departments of Molecular and Experimental Medicine and Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA
Proc Natl Acad Sci U S A 102:9294-9. 2005
..This system provides a powerful tool for the analysis of host-virus interactions that should facilitate the discovery of antiviral drugs and vaccines for this important human pathogen...
- Five-vertebrate ChIP-seq reveals the evolutionary dynamics of transcription factor binding
Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK
Science 328:1036-40. 2010
..Our results reveal large interspecies differences in transcriptional regulation and provide insight into regulatory evolution...
- MatInspector and beyond: promoter analysis based on transcription factor binding sites
Genomatix Software GmbH Landsberger Strasse 6, 80339 München, Germany
Bioinformatics 21:2933-42. 2005
..We describe a number of programs based on MatInspector allowing in-depth promoter analysis (DiAlignTF, FrameWorker) and targeted design of regulatory sequences (SequenceShaper)...
- An oestrogen-receptor-alpha-bound human chromatin interactome
Melissa J Fullwood
Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore 138672
Nature 462:58-64. 2009
..We propose that chromatin interactions constitute a primary mechanism for regulating transcription in mammalian genomes...
- Abscisic acid inhibits type 2C protein phosphatases via the PYR/PYL family of START proteins
Sang Youl Park
Department of Botany and Plant Sciences, University of California at Riverside, Riverside, CA 92521, USA
Science 324:1068-71. 2009
..Our results illustrate the power of the chemical genetic approach for sidestepping genetic redundancy...
- Mdm2 promotes the rapid degradation of p53
Lautenberg Center for General and Tumor Immunology, The Hebrew University Haddassah Medical School, Jerusalem, Israel
Nature 387:296-9. 1997
..During recovery from DNA damage, maximal Mdm2 induction coincides with rapid p53 loss. We propose that the Mdm2-promoted degradation of p53 provides a new mechanism to ensure effective termination of the p53 signal...
- p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy
Biochemistry Department, Institute of Medical Biology, University of Tromsø, 9037 Tromsø, Norway
J Biol Chem 282:24131-45. 2007
..In fact, p62 bodies and these structures are indistinguishable. Taken together, our results clearly suggest that p62 is required both for the formation and the degradation of polyubiquitin-containing bodies by autophagy...
- Purified human BRCA2 stimulates RAD51-mediated recombination
Ryan B Jensen
Department of Microbiology, University of California, Davis, California 95616, USA
Nature 467:678-83. 2010
- 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
- Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis
Jesper V Olsen
Department of Proteomics and Signal Transduction, Max Planck Institute for Biochemistry, Am Klopferspitz 18, D 82152 Martinsried near Munich, Germany
Sci Signal 3:ra3. 2010
..In particular, nuclear proteins and proteins involved in regulating metabolic processes have high phosphorylation site occupancy in mitosis. This suggests that these proteins may be inactivated by phosphorylation in mitotic cells...
- Structure of P-glycoprotein reveals a molecular basis for poly-specific drug binding
Stephen G Aller
Department of Molecular Biology, Scripps Research Institute, 10550 North Torrey Pines Road, CB105, La Jolla, CA 92037, USA
Science 323:1718-22. 2009
..The inward-facing conformation represents an initial stage of the transport cycle that is competent for drug binding...
- Core transcriptional regulatory circuitry in human embryonic stem cells
Laurie A Boyer
Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA
Cell 122:947-56. 2005
..These results provide new insights into the transcriptional regulation of stem cells and reveal how OCT4, SOX2, and NANOG contribute to pluripotency and self-renewal...
- The structural basis of lipopolysaccharide recognition by the TLR4-MD-2 complex
Beom Seok Park
Department of Chemistry, KAIST, Daejeon, 305 701, Korea
Nature 458:1191-5. 2009
..The TLR4-MD-2-LPS structure illustrates the remarkable versatility of the ligand recognition mechanisms employed by the TLR family, which is essential for defence against diverse microbial infection...
- The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis
P H Maxwell
Wellcome Trust Centre for Human Genetics, Oxford, UK
Nature 399:271-5. 1999
..Thus, constitutive HIF-1 activation may underlie the angiogenic phenotype of VHL-associated tumours. The pVHL/HIF-1 interaction provides a new focus for understanding cellular oxygen sensing...
- Recognition of trimethylated histone H3 lysine 4 facilitates the recruitment of transcription postinitiation factors and pre-mRNA splicing
Robert J Sims
Department of Biochemistry, New York University School of Medicine, New York, NY 10016, USA
Mol Cell 28:665-76. 2007
..These findings suggest that methylated H3K4 serves to facilitate the competency of pre-mRNA maturation through the bridging of spliceosomal components to H3K4me3 via CHD1...
- Developmental roles of 21 Drosophila transcription factors are determined by quantitative differences in binding to an overlapping set of thousands of genomic regions
Genomics Division, Lawrence Berkeley National Laboratory, Cyclotron Road MS 84 181, Berkeley, CA 94720, USA
Genome Biol 10:R80. 2009
- Systematic analysis of human protein complexes identifies chromosome segregation proteins
James R A Hutchins
Research Institute of Molecular Pathology IMP, Dr Bohr Gasse 7, A 1030 Vienna, Austria
Science 328:593-9. 2010
..The approaches we describe here are generally applicable to high-throughput follow-up analyses of phenotypic screens in mammalian cells...
- A semiempirical free energy force field with charge-based desolvation
Department of Molecular Biology, Scripps Research Institute, La Jolla, California 92102, USA
J Comput Chem 28:1145-52. 2007
..The force field shows improvement in redocking simulations over the previous AutoDock3 force field...
- Genome-wide analysis of ETS-family DNA-binding in vitro and in vivo
Gong Hong Wei
Public Health Genomics Unit, National Institute for Health and Welfare THL and Genome Scale Biology Program, Institute of Biomedicine and High Throughput Center, University of Helsinki, Biomedicum, Helsinki, Finland
EMBO J 29:2147-60. 2010
..The results indicate that even relatively small differences in in vitro binding specificity of a TF contribute to site selectivity in vivo...
- Design and analysis of ChIP-seq experiments for DNA-binding proteins
Peter V Kharchenko
Center for Biomedical Informatics, Harvard Medical School, 10 Shattuck St, Boston, Massachusetts 02115, USA
Nat Biotechnol 26:1351-9. 2008
..We also analyze the relationship between the depth of sequencing and characteristics of the detected binding positions, and provide a method for estimating the sequencing depth necessary for a desired coverage of protein binding sites.
- SIR2 and SIR4 interactions differ in core and extended telomeric heterochromatin in yeast
Department of Biological Chemistry, University of California, Los Angeles 90095, USA
Genes Dev 11:83-93. 1997
..RAP1 binding at the core region is unaffected by SIR3 overproduction and RAP1 shows no evidence of spreading. Thus, we propose that the structure of core telomeric heterochromatin differs from that extended by SIR3...
- Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus
Department of Biochemistry, University of Lausanne, BIL Biomedical Research Center, Chemin des Boveresses 155, CH 1066 Epalinges, Switzerland
Nature 437:1167-72. 2005
..Cardif thus functions as an adaptor, linking the cytoplasmic dsRNA receptor RIG-I to the initiation of antiviral programmes...
- Benchmarking sets for molecular docking
Department of Pharmaceutical Chemistry, University of California San Francisco, QB3 Building, 1700 4th Street, Box 2550, San Francisco, California 94143-2550, USA
J Med Chem 49:6789-801. 2006
..DUD is freely available online as a benchmarking set for docking at http://blaster.docking.org/dud/...
- Global, in vivo, and site-specific phosphorylation dynamics in signaling networks
Jesper V Olsen
Center for Experimental Bioinformatics, Department of Biochemistry and Molecular Biology, University of Southern Denmark, DK-5230 Odense, Denmark
Cell 127:635-48. 2006
..The dynamic phosphoproteome provides a missing link in a global, integrative view of cellular regulation...
- The 2.6 angstrom crystal structure of a human A2A adenosine receptor bound to an antagonist
Veli Pekka Jaakola
Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037 USA
Science 322:1211-7. 2008
- Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes
Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA
Science 300:1542-8. 2003
..Our data suggest that RPA-coated ssDNA is the critical structure at sites of DNA damage that recruits the ATR-ATRIP complex and facilitates its recognition of substrates for phosphorylation and the initiation of checkpoint signaling...
- A dual-kinase mechanism for Wnt co-receptor phosphorylation and activation
Neurobiology Program, Children's Hospital Boston, Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115, USA
Nature 438:873-7. 2005
- The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression
Instituto de Investigaciones Biomedicas, Arturo Duperier 4, 28029 Madrid, Spain
Nat Cell Biol 2:76-83. 2000
..Snail may thus be considered as a marker for malignancy, opening up new avenues for the design of specific anti-invasive drugs...
- Molecular architecture of native HIV-1 gp120 trimers
Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA
Nature 455:109-13. 2008
..Our findings elucidate the structure and conformational changes of trimeric HIV-1 gp120 relevant to antibody neutralization and attachment to target cells...
- Glycogen synthase kinase-3beta regulates cyclin D1 proteolysis and subcellular localization
J A Diehl
Howard Hughes Medical Institute, St Jude Children s Research Hospital, Memphis, Tennessee 38105 USA
Genes Dev 12:3499-511. 1998
..Therefore, phosphorylation and proteolytic turnover of cyclin D1 and its subcellular localization during the cell division cycle are linked through the action of GSK-3beta...
- MeCP2 binding to DNA depends upon hydration at methyl-CpG
Kok Lian Ho
School of Biological Sciences, University of Edinburgh, King s Buildings, Mayfield Road, Edinburgh EH9 3JR, UK
Mol Cell 29:525-31. 2008
..The MeCP2-DNA complex also identifies a unique structural role for T158, the residue most commonly mutated in Rett syndrome...
- Visualization of protein interactions in living plant cells using bimolecular fluorescence complementation
Institut fur Botanik und Botanischer Garten, Molekulare Entwicklungsbiologie der Pflanzen, Universitat Munster, Schlossplatz 4, 48149 Munster, Germany
Plant J 40:428-38. 2004
..Consequently, the BiFC approach should significantly facilitate the visualization of the subcellular sites of protein interactions under conditions that closely reflect the normal physiological environment...
- Diverse RNA-binding proteins interact with functionally related sets of RNAs, suggesting an extensive regulatory system
Daniel J Hogan
Department of Biochemistry, Stanford University School of Medicine, Stanford, California, United States of America
PLoS Biol 6:e255. 2008
..These results strongly suggest that combinatorial binding of RBPs to specific recognition elements in mRNAs is a pervasive mechanism for multi-dimensional regulation of their post-transcriptional fate...
- Neurexins induce differentiation of GABA and glutamate postsynaptic specializations via neuroligins
Ethan R Graf
Department of Anatomy and Neurobiology, Washington University School of Medicine, 660 S Euclid Avenue, St Louis, MO 63110, USA
Cell 119:1013-26. 2004
- MDM2 inhibitors for cancer therapy
Lyubomir T Vassilev
Discovery Oncology, Roche Research Center, Hoffmann La Roche Inc, Nutley, NJ 07110, USA
Trends Mol Med 13:23-31. 2007
..Here, the new developments in the quest for pharmacological p53 activators are reviewed with an emphasis on small-molecule inhibitors of the p53-MDM2 interaction...
- Frequent gain and loss of functional transcription factor binding sites
Scott W Doniger
Computational Biology Program, Washington University School of Medicine, St Louis, Missouri, United States of America
PLoS Comput Biol 3:e99. 2007
..The frequent gain and loss of TFBSs implies that cis-regulatory sequences are labile and, in the absence of turnover, may contribute to species-specific patterns of gene expression...
- A flagellin-induced complex of the receptor FLS2 and BAK1 initiates plant defence
Zurich Basel Plant Science Center, Botanical Institute, University of Basel, Hebelstrasse 1, 4056 Basel, Switzerland
Nature 448:497-500. 2007
..Thus, BAK1 is not only associated with developmental regulation through the plant hormone receptor BRI1 (refs 6,7), but also has a functional role in PRR-dependent signalling, which initiates innate immunity...
- Preferential associations between co-regulated genes reveal a transcriptional interactome in erythroid cells
Laboratory of Chromatin and Gene Expression, Babraham Research Campus, Cambridge, UK
Nat Genet 42:53-61. 2010
..Our results establish a new gene expression paradigm, implying that active co-regulated genes and their regulatory factors cooperate to create specialized nuclear hot spots optimized for efficient and coordinated transcriptional control...
- Curvature of clathrin-coated pits driven by epsin
Marijn G J Ford
MRC Laboratory of Molecular Biology, Cambridge, UK
Nature 419:361-6. 2002
..We propose that this helix is inserted into one leaflet of the lipid bilayer, inducing curvature. On lipid monolayers epsin alone is sufficient to facilitate the formation of clathrin-coated invaginations...
- Specificity and stability in topology of protein networks
Department of Physics, Brookhaven National Laboratory, Upton, NY 11973, USA
Science 296:910-3. 2002
..This effect decreases the likelihood of cross talk between different functional modules of the cell and increases the overall robustness of a network by localizing effects of deleterious perturbations...
- Antidepressant specificity of serotonin transporter suggested by three LeuT-SSRI structures
Kimmel Center for Biology and Medicine at the Skirball Institute of Biomolecular Medicine, Department of Cell Biology, New York University School of Medicine, New York, New York, USA
Nat Struct Mol Biol 16:652-7. 2009
..Thus, the specificity of SERT for SSRIs is dependent largely on interaction of the drug halogens with the protein's HBP...
- The pharmacology of mTOR inhibition
David A Guertin
Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02141, USA
Sci Signal 2:pe24. 2009
..Here, we summarize exciting findings regarding mTOR signaling and the outlook for mTOR inhibitors as tools to study the mTOR pathway and as drugs in the clinic...
- Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1
Joseph T Rodgers
Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
Nature 434:113-8. 2005
..Thus, we have identified a molecular mechanism whereby SIRT1 functions in glucose homeostasis as a modulator of PGC-1alpha. These findings have strong implications for the basic pathways of energy homeostasis, diabetes and lifespan...
- A comprehensive map of insulator elements for the Drosophila genome
Institute for Genomics and Systems Biology, Department of Human Genetics, and Department of Ecology and Evolution, University of Chicago, Chicago, Illinois, USA
PLoS Genet 6:e1000814. 2010
..Together, these results provide a map demarcating the boundaries of gene regulatory units and a framework for understanding insulator function during the development and evolution of Drosophila...
- In-frame deletion in a novel centrosomal/ciliary protein CEP290/NPHP6 perturbs its interaction with RPGR and results in early-onset retinal degeneration in the rd16 mouse
The Jackson Laboratory, Bar Harbor, ME 04609, USA
Hum Mol Genet 15:1847-57. 2006
..Our findings suggest a critical function for CEP290 in ciliary transport and provide insights into the mechanism of early-onset photoreceptor degeneration...
- Structural basis for recognition of H3K4 methylation status by the DNA methyltransferase 3A ATRX-DNMT3-DNMT3L domain
Department of Molecular Engineering, Graduate School of Engineering, Kyoto University, Kyoto Daigaku Katsura, Nishikyo ku, Kyoto 615 8510, Japan
EMBO Rep 10:1235-41. 2009
..These results indicate that de novo DNA methylation by DNMT3A requires the alteration of chromatin structure...
- p53AIP1, a potential mediator of p53-dependent apoptosis, and its regulation by Ser-46-phosphorylated p53
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Japan
Cell 102:849-62. 2000
..Our results suggest that p53AIP1 is likely to play an important role in mediating p53-dependent apoptosis, and phosphorylation of Ser-46 regulates the transcriptional activation of this apoptosis-inducing gene...
- Cracking the RNA polymerase II CTD code
Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK
Trends Genet 24:280-8. 2008
..How and when is the code written and read? How does it contribute to transcription and coordinate RNA processing?..
- Structure of Escherichia coli Hfq bound to polyriboadenylate RNA
Todd M Link
Department of Biochemistry and Molecular Biology, University of Texas, MD Anderson Cancer Center, Houston, TX 77030 4009, USA
Proc Natl Acad Sci U S A 106:19292-7. 2009
..The abundance of (A-R-N)(4) and (A-R-N)(5) triplet repeats in the E. coli genome suggests additional RNA targets for Hfq. Further, the structure provides insight into Hfq-mediated sRNA-mRNA annealing and the role of Hfq in RNA decay...
- Cyclic di-GMP allosterically inhibits the CRP-like protein (Clp) of Xanthomonas axonopodis pv. citri
Jason L Leduc
Department of Bacteriology, 1550 Linden Drive, University of Wisconsin Madison, Madison, WI 53706, USA
J Bacteriol 191:7121-2. 2009
..We show that unlike the DNA-binding activity of other members of this family, the DNA-binding activity of Clp is allosterically inhibited by its effector and that cyclic di-GMP serves as that effector at physiological concentrations...
- Predicting protein ligand binding sites by combining evolutionary sequence conservation and 3D structure
John A Capra
Department of Computer Science, Princeton University, Princeton, New Jersey, United States of America
PLoS Comput Biol 5:e1000585. 2009
..Data, source code, and prediction visualizations are available on the ConCavity web site (http://compbio.cs.princeton.edu/concavity/)...
- The mammalian clock component PERIOD2 coordinates circadian output by interaction with nuclear receptors
Department of Medicine, Unit of Biochemistry, University of Fribourg, 1700 Fribourg, Switzerland
Genes Dev 24:345-57. 2010
..The concept that PER2 may propagate clock information to metabolic pathways via nuclear receptors adds an important facet to the clock-dependent regulation of biological networks...
- Dynamic strength of molecular adhesion bonds
Department of Physics, University of British Columbia, Vancouver, Canada
Biophys J 72:1541-55. 1997
..Balsera, Y. Oono, and K. Schulten. 1997. Molecular dynamics study of unbinding of the avidin-biotin complex. Biophys. J., this issue), we describe how Brownian dynamics can help bridge the gap between molecular dynamics and probe tests...
- Circadian clock feedback cycle through NAMPT-mediated NAD+ biosynthesis
Kathryn Moynihan Ramsey
Department of Medicine, Northwestern University Feinberg School of Medicine, 2200 Campus Drive, Evanston, IL 60208 3500, USA
Science 324:651-4. 2009
..In turn, the circadian transcription factor CLOCK binds to and up-regulates Nampt, thus completing a feedback loop involving NAMPT/NAD+ and SIRT1/CLOCK:BMAL1...
- Improved protein-ligand docking using GOLD
Marcel L Verdonk
Astex Technology, Ltd, Cambridge, United Kingdom
Proteins 52:609-23. 2003
..Even at docking speeds of around 1-2 min/compound, the Goldscore function predicts binding energies with a standard deviation of approximately 10.5 kJ/mol...
- Protein dynamics and conformational disorder in molecular recognition
Program in Molecular Structure and Function, Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada
J Mol Recognit 23:105-16. 2010
..The nature of these interactions is not well understood yet but advancements in the structural characterization of disordered states will help us gain insights into their function and their implications for health and disease...
- Activation of transcription through the ligand-binding pocket of the orphan nuclear receptor ultraspiracle
Molecular and Cellular Biology Section, Department of Biology, and Graduate Center for Toxicology, Chandler Medical Center, University of Kentucky Lexington, USA
Eur J Biochem 269:6026-36. 2002
..The demonstration here of these functional capacities of USP in a transcriptional activation pathway has significant implications for current paradigms of USP action that do not include for USP a ligand-binding activity...
- Topography for independent binding of alpha-helical and PPII-helical ligands to a peroxisomal SH3 domain
EMBL Hamburg, c o Deutsches Elektronen Synchrotron, Notkestrasse 85, D 22603 Hamburg, Germany
Mol Cell 10:1007-17. 2002
..Mutations in the Pex13p SH3 domain that abolish interactions within the Pex13p-Pex5p interface specifically impair PTS1-dependent protein import into yeast peroxisomes...
- Yeast epiarginase regulation, an enzyme-enzyme activity control: identification of residues of ornithine carbamoyltransferase and arginase responsible for enzyme catalytic and regulatory activities
Mohamed El Alami
Universite Libre de Bruxelles, Laboratoire de Microbiologie and Institut de Recherches Microbiologiques J M Wiame, Ave Emile Gryzon 1, Brussels 1070, Belgium
J Biol Chem 278:21550-8. 2003
- The nucleotide-binding site of human sphingosine kinase 1
Stuart M Pitson
Hanson Institute, Division of Human Immunology, Institute of Medical and Veterinary Science, Frome Road, Adelaide SA 5000, Australia
J Biol Chem 277:49545-53. 2002
..It does, however, share some sequence and likely structural similarity with the highly conserved glycine-rich loop, which is known to be involved in anchoring and positioning the nucleotide in the catalytic site of many protein kinases...
- Mapping the Galpha13 binding interface of the rgRGS domain of p115RhoGEF
Department of Biochemistry, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
J Biol Chem 278:9912-9. 2003
..This suggests that the rgRGS domain may serve a structural or allosteric role in the regulation of the nucleotide exchange activity of p115RhoGEF on Rho by Galpha(13)...
- Three-dimensional localization of divergent region 3 of the ryanodine receptor to the clamp-shaped structures adjacent to the FKBP binding sites
Cardiovascular Research Group, Department of Physiology, University of Calgary, Alberta T2N 4N1, Canada
J Biol Chem 278:14211-8. 2003
..6 binding. These results provide a structural basis for the role of the DR3 region in excitation-contraction coupling and in channel regulation...
- The distal hinge of the reactive site loop and its proximity: a target to modulate plasminogen activator inhibitor-1 activity
A P Bijnens
Laboratory for Pharmaceutical Biology and Phytopharmacology, Faculty of Pharmaceutical Sciences, Katholieke Universiteit Leuven, Belgium
J Biol Chem 276:44912-8. 2001
- The integrity of a cholesterol-binding pocket in Niemann-Pick C2 protein is necessary to control lysosome cholesterol levels
Dennis C Ko
Department of Developmental Biology, Beckman Center B300, 279 Campus Drive, Stanford University School of Medicine, Stanford, CA 94305 5329, USA
Proc Natl Acad Sci U S A 100:2518-25. 2003
..On the basis of evolutionary analysis and mutagenesis, three other regions of the NPC2 protein emerged as important, including one required for efficient secretion...
- Structure of a cholesterol-binding protein deficient in Niemann-Pick type C2 disease
Center for Advanced Biotechnology and Medicine, Howard Hughes Medical Institute, University of Medicine and Dentistry of New Jersey Robert Wood Johnson Medical School, 679 Hoes Lane, Piscataway, NJ 08854, USA
Proc Natl Acad Sci U S A 100:2512-7. 2003
..We propose that this region represents the incipient cholesterol-binding site that dilates to accommodate an approximately 740-A(3) cholesterol molecule...
- Electrostatic modulation in steroid receptor recruitment of LXXLL and FXXLF motifs
Laboratories for Reproductive Biology, Department of Biochemistry and Biophysics, University of North Carolina, 374 Medical Sciences Research Building, Chapel Hill, NC 27599 7500, USA
Mol Cell Biol 23:2135-50. 2003
..The data suggest a model whereby coactivator recruitment to the receptor AF2 surface is initiated by complementary charge interactions that reflect a reversal of the acidic activation domain-coactivator interaction model...
- Structural basis of the KcsA K(+) channel and agitoxin2 pore-blocking toxin interaction by using the transferred cross-saturation method
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, 113-0033 Tokyo, Japan
Structure 11:1381-92. 2003
..The TCS method utilized here is applicable not only for the channels, which are complexed with other inhibitors, but also with a variety of regulatory molecules, and provides important information about their interface in solution...
- A corresponding tyrosine residue in the C2/factor B type A domain is a hot spot in the decay acceleration of the complement C3 convertases
Lisa A Kuttner-Kondo
Case Western Reserve University, Institute of Pathology, Cleveland, Ohio 44106, USA
J Biol Chem 278:52386-91. 2003
- Spatial approximation between two residues in the mid-region of secretin and the amino terminus of its receptor. Incorporation of seven sets of such constraints into a three-dimensional model of the agonist-bound secretin receptor
Cancer Center and the Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic Scottsdale, Scottsdale, Arizona 85259, USA
J Biol Chem 278:48300-12. 2003
..This provides clear insights into the molecular basis of natural ligand binding and supplies testable hypotheses regarding the molecular basis of activation of this receptor...
- Functional importance of polar and charged amino acid residues in transmembrane helix 14 of multidrug resistance protein 1 (MRP1/ABCC1): identification of an aspartate residue critical for conversion from a high to low affinity substrate binding state
Da Wei Zhang
Division of Cancer Biology and Genetics, Cancer Research Institute, Queen s University, Kingston, Ontario K7L 3N6, Canada
J Biol Chem 278:46052-63. 2003
- Molecular determinants of the balance between co-repressor and co-activator recruitment to the retinoic acid receptor
Department of Biochemistry and Molecular Biology, Research Center for Molecular Medicine, University of Debrecen, Medical and Health Science Center, Nagyerdei krt. 98, Debrecen H-4012, Hungary
J Biol Chem 278:43797-806. 2003
..These data suggest that residues in the close vicinity of H12 regulate cofactor affinity and determine the basal activity of receptors...
- Constitutive activation of the angiotensin II type 1 receptor alters the spatial proximity of transmembrane 7 to the ligand-binding pocket
Antony A Boucard
Department of Pharmacology, Faculty of Medicine, Universite de Sherbrooke, Sherbrooke, Quebec J1H 5N4, Canada
J Biol Chem 278:36628-36. 2003
..These studies support accumulating evidence whereby elements of TM7 of class A GPCRs promote activation of the receptor through structural rearrangements...
- The fourth blade within the beta-propeller is involved specifically in C3bi recognition by integrin alpha M beta 2
Department of Vascular Biology, Jerome H Holland Laboratory for the Biomedical Sciences, American Red Cross, Rockville, Maryland 20855, USA
J Biol Chem 278:34395-402. 2003
- Grb2-independent recruitment of Gab1 requires the C-terminal lobe and structural integrity of the Met receptor kinase domain
Lisa S Lock
Department of Biochemistry, Molecular Oncology Group, McGill University Health Centre, Montreal, Quebec H3A 1A1, Canada
J Biol Chem 278:30083-90. 2003
..We propose that Gab1 and the Met receptor interact in a novel manner, such that the activated kinase domain of Met and the negative charge of phosphotyrosine 1349 engage the Gab1 MBD as an extended peptide ligand...
- Sequences within domain II of the urokinase receptor critical for differential ligand recognition
Department of Vascular Biology, Jerome H Holland Laboratory for the Biomedical Sciences, American Red Cross, Rockville, Maryland 20855, USA
J Biol Chem 278:29925-32. 2003
..Altogether, our data demonstrated that uPAR D2 contains two distinct ligand binding sites for uPA and Vn. Such information will help us better understand the complex roles of uPAR in cell adhesion, migration, and tumor metastasis...
- A Cortactin-CD2-associated protein (CD2AP) complex provides a novel link between epidermal growth factor receptor endocytosis and the actin cytoskeleton
Danielle K Lynch
Cancer Research Program, Garvan Institute of Medical Research, St Vincent s Hospital, Sydney, New South Wales 2010, Australia
J Biol Chem 278:21805-13. 2003
..Therefore, by binding both CD2AP and the Arp2/3 complex, cortactin links receptor endocytosis to actin polymerization, which may facilitate the trafficking of internalized growth factor receptors...
- Nucleotide control of interdomain interactions in the conformational reaction cycle of SecA
John F Hunt
Department of Biological Sciences, 702A Fairchild Center, MC2434, Columbia University, New York, NY 10027, USA
Science 297:2018-26. 2002
- The pro-apoptotic function of death-associated protein kinase is controlled by a unique inhibitory autophosphorylation-based mechanism
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel
J Biol Chem 276:47460-7. 2001
..We propose that this unique mechanism of auto-inhibition evolved to impose a locking device, which keeps death-associated protein kinase silent in healthy cells and ensures its activation only in response to apoptotic signals...
- Molecular determinants of high affinity binding to group III metabotropic glutamate receptors
Department of Pharmaceutical Sciences, University of Toronto, 19 Russell Street, Toronto, Ontario M5S 2S2, Canada
J Biol Chem 277:7333-40. 2002
..Our results define a microenvironment within the binding pocket that encompasses several positively charged amino acids that recognize the negatively charged phosphonate group of l-AP4 or the endogenous compound l-serine-O-phosphate...
- Selection and structure of ion-selective ligands for platelet integrin alpha IIb(beta) 3
Jeffrey W Smith
Program on Cell Adhesion, Cancer Research Center, The Burnham Institute, La Jolla, California 92037, USA
J Biol Chem 277:10298-305. 2002
..All peptides formed turns, with the RGD motif at the apex. The Mg(2+)-selected peptides contained a unique basic patch that protrudes from the base of the turn...
- Determinants of ligand specificity in groups I and IV WW domains as studied by surface plasmon resonance and model building
Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan
J Biol Chem 277:10173-7. 2002
..We propose that this configuration of Loop I (referred to as the "p patch") is necessary for binding Group IV ligands and that it can be used to predict the specificity and functions of other WW domains...
- A molecular basis for the selective recognition of 2-hydroxy-dATP and 8-oxo-dGTP by human MTH1
Division of Neurofunctional Genomics, Medical Institute of Bioregulation, Kyushu University and CREST, Japan Science and Technology Corporation, Fukuoka 812 8582, Japan
J Biol Chem 277:8579-87. 2002
- Affinity alkylation of the Trp-B4 residue of the beta -subunit of the glutaryl 7-aminocephalosporanic acid acylase of Pseudomonas sp. 130
Laboratory of Microbial Molecular Physiology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200032, China
J Biol Chem 277:10256-64. 2002
..Therefore, a large conformational alteration during inhibitor binding and transition state formation is likely and suggests that a major conformational change is induced by substrate binding during the course of catalysis...
- NMR structural analysis of alpha-bungarotoxin and its complex with the principal alpha-neurotoxin-binding sequence on the alpha 7 subunit of a neuronal nicotinic acetylcholine receptor
Department of Molecular Pharmacology, Brown University, Providence, Rhode Island 02912, USA
J Biol Chem 277:12406-17. 2002
..The disulfide-rich core of alpha-bungarotoxin is suggested to be tilted in the direction of the membrane surface with finger II extending into the proposed ligand-binding cavity...
- The COOH terminus of arylamine N-acetyltransferase from Salmonella typhimurium controls enzymic activity
Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, United Kingdom
J Biol Chem 277:12175-81. 2002
..Both truncation mutants, however, hydrolyze Ac-CoA even in the absence of arylamine substrate, illustrating that the C-terminal undecapeptide controls hydrolysis of Ac-CoA by NAT from S. typhimurium...
- Crystal structure of rat short chain acyl-CoA dehydrogenase complexed with acetoacetyl-CoA: comparison with other acyl-CoA dehydrogenases
Kevin P Battaile
Department of Biochemistry, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA
J Biol Chem 277:12200-7. 2002
..Ten reported pathogenic human mutations and two polymorphisms have been mapped onto the structure of short chain acyl-CoA dehydrogenase. None of the mutations directly affect the binding cavity or intersubunit interactions...
- Identification of the binding site for fibrinogen recognition peptide gamma 383-395 within the alpha(M)I-domain of integrin alpha(M)beta2
V P Yakubenko
Joseph J. Jacobs Center for Thrombosis and Vascular Biology and the Department of Molecular Cardiology, Lerner Research Institute, Cleveland, Ohio 44195, USA
J Biol Chem 276:13995-4003. 2001
- A copper metallochaperone for photosynthesis and respiration reveals metal-specific targets, interaction with an importer, and alternative sites for copper acquisition
Department of Biochemistry and Genetics, Medical School, University of Newcastle, Newcastle upon Tyne NE2 4HH, United Kingdom
J Biol Chem 277:5490-7. 2002
..Conversely, activity in Deltaatx1DeltactaA was less than in either respective single mutant, revealing that Atx1 can function without the major copper importer and consistent with a role in recycling endogenous copper...
- Glycosaminoglycan binding properties of the myxoma virus CC-chemokine inhibitor, M-T1
B T Seet
Departments of Microbiology and Immunology and Biochemistry, The University of Western Ontario, London, Ontario, Canada N6A 5C1
J Biol Chem 276:30504-13. 2001
- Cysteine 144 in the third transmembrane domain of the creatine transporter is located close to a substrate-binding site
J R Dodd
Protein Structure and Function Research Group, School of Biological Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand
J Biol Chem 276:46983-8. 2001
..Our results indicate that cysteine 144 is close to the binding site or part of a permeation channel for creatine...
- Unusual binding properties of the SH3 domain of the yeast actin-binding protein Abp1: structural and functional analysis
Department of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica, 00133 Roma, Italy
J Biol Chem 277:5290-8. 2002
..We have shown by site-directed mutagenesis that one of these negatively charged side chains may be the key determinant for the preference for non-classical ligands...
- Identification of ligand-binding site III on the immunoglobulin-like domain of the granulocyte colony-stimulating factor receptor
J E Layton
Ludwig Institute for Cancer Research, Melbourne Tumour Biology Branch and the Cooperative Research Centre for Cellular Growth Factors, Parkville, Victoria 3050, Australia
J Biol Chem 276:36779-87. 2001
..A model of the tetrameric G-CSF.G-CSF-R complex was prepared, based on the viral interleukin-6.gp130 complex, which explains these and previously published data...
- Mutations to Gly2370, Gly2373 or Gly2375 in malignant hyperthermia domain 2 decrease caffeine and cresol sensitivity of the rabbit skeletal-muscle Ca2+-release channel (ryanodine receptor isoform 1)
G G Du
Banting and Best Department of Medical Research, University of Toronto, Charles H. Best Institute, 112 College Street, Toronto, Ontario M5G 1L6, Canada
Biochem J 360:97-105. 2001
..Thus amino acids 2163-2458 form a regulatory domain (malignant hyperthermia regulatory domain 2) that regulates caffeine and 4-chloro-m-cresol sensitivity of RyR1...
- Molecular determinants of receptor binding and signaling by the CX3C chemokine fractalkine
L S Mizoue
Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA
J Biol Chem 276:33906-14. 2001
..Comparison of the binding surfaces of fractalkine and the CC chemokine MCP-1 reveals structural details that may account for their dual recognition by US28 and their selective recognition by host receptors...
- The biologically crucial C terminus of cholecystokinin and the non-peptide agonist SR-146,131 share a common binding site in the human CCK1 receptor. Evidence for a crucial role of Met-121 in the activation process
INSERM Unite 531, Institut Louis Bugnard, Centre Hospitalier Universitaire Rangueil, Bat L3, 31403 Toulouse Cedex 4, France
J Biol Chem 277:7546-55. 2002
..e. Met-Asp-Phe-NH(2). These new and important insights will serve to better understand the activation process of CCK1R and to design or optimize ligands...