guanosine diphosphate

Summary

Summary: Guanosine 5'-(trihydrogen diphosphate). A guanine nucleotide containing two phosphate groups esterified to the sugar moiety. Synonyms: GRPP; guanosine pyrophosphate.

Top Publications

  1. ncbi The guanine nucleotide-binding switch in three dimensions
    I R Vetter
    , 44227 Dortmund, Germany
    Science 294:1299-304. 2001
  2. ncbi The Ras-RasGAP complex: structural basis for GTPase activation and its loss in oncogenic Ras mutants
    K Scheffzek
    Max Planck Institut fur molekulare Physiologie, Abteilung Strukturelle Biologie, Rheinlanddamm 201, 44139 Dortmund, Germany
    Science 277:333-8. 1997
  3. ncbi A novel Rab5 GDP/GTP exchange factor complexed to Rabaptin-5 links nucleotide exchange to effector recruitment and function
    H Horiuchi
    European Molecular Biology Laboratory, Heidelberg, Germany
    Cell 90:1149-59. 1997
  4. ncbi It takes two to tango: regulation of G proteins by dimerization
    Raphael Gasper
    Max Planck Institut fur molekulare Physiologie, Abteilung Strukturelle Biologie, Dortmund, Germany
    Nat Rev Mol Cell Biol 10:423-9. 2009
  5. ncbi Hydrolysis of GTP by elongation factor G drives tRNA movement on the ribosome
    M V Rodnina
    Institute of Molecular Biology, University of Witten Herdecke, Germany
    Nature 385:37-41. 1997
  6. ncbi An elongation factor G-induced ribosome rearrangement precedes tRNA-mRNA translocation
    Andreas Savelsbergh
    Institute of Molecular Biology, University of Witten Herdecke, 58448 Witten, Germany
    Mol Cell 11:1517-23. 2003
  7. ncbi Structure of the Rho family GTP-binding protein Cdc42 in complex with the multifunctional regulator RhoGDI
    G R Hoffman
    Department of Molecular Medicine, Veterinary Medical Center, Cornell University, Ithaca, New York 14853, USA
    Cell 100:345-56. 2000
  8. pmc Structural flexibility of the G alpha s alpha-helical domain in the beta2-adrenoceptor Gs complex
    Gerwin H Westfield
    Life Sciences Institute and Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI 48109, USA
    Proc Natl Acad Sci U S A 108:16086-91. 2011
  9. pmc Mapping the nucleotide and isoform-dependent structural and dynamical features of Ras proteins
    Alemayehu A Gorfe
    Department of Chemistry and Biochemistry and Center for Theoretical Biological Physics, University of California San Diego, La Jolla, CA 92093 0365, USA
    Structure 16:885-96. 2008
  10. ncbi The GTPase superfamily: conserved structure and molecular mechanism
    H R Bourne
    Department of Pharmacology, University of California, San Francisco 94143 0450
    Nature 349:117-27. 1991

Research Grants

  1. Mechanism of G protein Activation by Ric-8A
    Stephen R Sprang; Fiscal Year: 2013
  2. NEUROFIBROMATOSIS TYPE 1 GENE REGULATES MYELOPOIESIS
    DAVID CLAPP; Fiscal Year: 2001
  3. KINETICS AND CHEMISTRY OF ALLOSTERIC INTERACTIONS
    Thomas Smith; Fiscal Year: 1992
  4. STRUCTURAL BASIS FOR BINDING TO G PROTEIN BETA GAMMA
    Alan Smrcka; Fiscal Year: 2007
  5. REGULATION OF SUPEROXIDE PRODUCTION BY HUMAN NEUTROPHILS
    Jeffrey Friedman; Fiscal Year: 2007
  6. Novel Pathways of Polyphosphate Synthesis
    Arthur Kornberg; Fiscal Year: 2005
  7. Southeast Collaboratory for High-Field Biomolecular NMR
    James Prestegard; Fiscal Year: 2006
  8. RECEPTOR COUPLING TO G12 AND G13
    David Manning; Fiscal Year: 2006
  9. Mechanisms of Nucleotide Release by Airway Epithelia
    Eduardo Lazarowski; Fiscal Year: 2006
  10. Reactive Oxygen Species in Anti-Viral Airway Host Defense
    Jeffrey Friedman; Fiscal Year: 2008

Detail Information

Publications258 found, 100 shown here

  1. ncbi The guanine nucleotide-binding switch in three dimensions
    I R Vetter
    , 44227 Dortmund, Germany
    Science 294:1299-304. 2001
    ..They act as molecular switches and timers that cycle between inactive guanosine diphosphate (GDP)-bound and active guanosine triphosphate (GTP)-bound states...
  2. ncbi The Ras-RasGAP complex: structural basis for GTPase activation and its loss in oncogenic Ras mutants
    K Scheffzek
    Max Planck Institut fur molekulare Physiologie, Abteilung Strukturelle Biologie, Rheinlanddamm 201, 44139 Dortmund, Germany
    Science 277:333-8. 1997
    The three-dimensional structure of the complex between human H-Ras bound to guanosine diphosphate and the guanosine triphosphatase (GTPase)-activating domain of the human GTPase-activating protein p120GAP (GAP-334) in the presence of ..
  3. ncbi A novel Rab5 GDP/GTP exchange factor complexed to Rabaptin-5 links nucleotide exchange to effector recruitment and function
    H Horiuchi
    European Molecular Biology Laboratory, Heidelberg, Germany
    Cell 90:1149-59. 1997
    ..This demonstrates that a soluble exchange factor coupled to a Rab effector translocates from cytosol to the membrane, where the complex stabilizes the GTPase in the active state...
  4. ncbi It takes two to tango: regulation of G proteins by dimerization
    Raphael Gasper
    Max Planck Institut fur molekulare Physiologie, Abteilung Strukturelle Biologie, Dortmund, Germany
    Nat Rev Mol Cell Biol 10:423-9. 2009
    ..We propose that the juxtaposition of the G domains of two monomers across the GTP-binding sites activates the biological function of these proteins and the GTPase reaction...
  5. ncbi Hydrolysis of GTP by elongation factor G drives tRNA movement on the ribosome
    M V Rodnina
    Institute of Molecular Biology, University of Witten Herdecke, Germany
    Nature 385:37-41. 1997
    ..By coupling the free energy of GTP hydrolysis to translocation, EF-G serves as a motor protein to drive the directional movement of transfer and messenger RNAs on the ribosome...
  6. ncbi An elongation factor G-induced ribosome rearrangement precedes tRNA-mRNA translocation
    Andreas Savelsbergh
    Institute of Molecular Biology, University of Witten Herdecke, 58448 Witten, Germany
    Mol Cell 11:1517-23. 2003
    ..These results indicate that the energy of GTP hydrolysis is utilized to promote the ribosome rearrangement and to bias spontaneous fluctuations within the ribosome-EF-G complex toward unidirectional movement of mRNA and tRNA...
  7. ncbi Structure of the Rho family GTP-binding protein Cdc42 in complex with the multifunctional regulator RhoGDI
    G R Hoffman
    Department of Molecular Medicine, Veterinary Medical Center, Cornell University, Ithaca, New York 14853, USA
    Cell 100:345-56. 2000
    ..The structural data demonstrate how GDIs serve as negative regulators of small GTP-binding proteins and how the isoprenoid moiety is utilized in this critical regulatory interaction...
  8. pmc Structural flexibility of the G alpha s alpha-helical domain in the beta2-adrenoceptor Gs complex
    Gerwin H Westfield
    Life Sciences Institute and Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI 48109, USA
    Proc Natl Acad Sci U S A 108:16086-91. 2011
    ..These data argue that the α-helical domain undergoes a nucleotide-dependent transition from a flexible to a conformationally stabilized state...
  9. pmc Mapping the nucleotide and isoform-dependent structural and dynamical features of Ras proteins
    Alemayehu A Gorfe
    Department of Chemistry and Biochemistry and Center for Theoretical Biological Physics, University of California San Diego, La Jolla, CA 92093 0365, USA
    Structure 16:885-96. 2008
    ..We identified a number of isoform-specific, long-range side chain interactions that define unique pathways of communication between the nucleotide binding site and the C terminus...
  10. ncbi The GTPase superfamily: conserved structure and molecular mechanism
    H R Bourne
    Department of Pharmacology, University of California, San Francisco 94143 0450
    Nature 349:117-27. 1991
    ....
  11. ncbi Crystal structure and functional analysis of the eukaryotic class II release factor eRF3 from S. pombe
    Chunguang Kong
    Laboratory of Macromolecular Structure, Institute of Molecular and Cell Biology, 30 Medical Drive, Singapore 117609, Japan
    Mol Cell 14:233-45. 2004
    ..The N-terminal extension, rich in acidic amino acids, blocks the proposed eRF1 binding site, potentially regulating eRF1 binding to eRF3 in a competitive manner...
  12. ncbi Kinetic analysis of interaction of eukaryotic release factor 3 with guanine nucleotides
    Vera P Pisareva
    Department of Microbiology and Immunology, State University of New York Downstate Medical Center, Brooklyn, New York 11203, USA
    J Biol Chem 281:40224-35. 2006
    ..Guanine nucleotide binding and exchange on eRF3, which therefore depends on stimulation by eRF1, is entirely different from that on prokaryotic RF3 and unusual among GTPases...
  13. pmc Kissing G domains of MnmE monitored by X-ray crystallography and pulse electron paramagnetic resonance spectroscopy
    Simon Meyer
    Department of Structural Biology, Max Planck Institute of Molecular Physiology, Dortmund, Germany
    PLoS Biol 7:e1000212. 2009
    ..They show the nucleotide-dependent dynamic movements of the G domains around two swivel positions relative to the rest of the protein, and they are of crucial importance for understanding the mechanistic principles of this GAD...
  14. pmc RhoGDIgamma: a GDP-dissociation inhibitor for Rho proteins with preferential expression in brain and pancreas
    C N Adra
    Harvard Institutes of Medicine, HIM955, Beth Israel Hospital, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA
    Proc Natl Acad Sci U S A 94:4279-84. 1997
    ..We propose that RhoGDI be renamed RhoGDIalpha and GDID4 be renamed RhoGDIbeta. The new GDI should widen the scope of investigation of this important class of regulatory protein...
  15. ncbi Crystal structure of ARF1*Sec7 complexed with Brefeldin A and its implications for the guanine nucleotide exchange mechanism
    Elena Mossessova
    Howard Hughes Medical Institute, Structural Biology Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
    Mol Cell 12:1403-11. 2003
    ..Thus, the Sec7 domain may act as a dual catalyst, facilitating both nucleotide release and conformational switching on ARF proteins...
  16. ncbi Crystal structure of intact elongation factor EF-Tu from Escherichia coli in GDP conformation at 2.05 A resolution
    H Song
    School of Biochemistry and Molecular Biology, University of Leeds, Leeds, LS2 9JT, UK
    J Mol Biol 285:1245-56. 1999
    ..Comparisons of the Mg2+ binding site with other guanine nucleotide binding proteins in GDP-bound forms show that the Mg2+ co-ordination patterns are well preserved among these structures...
  17. ncbi The nuclear transport factor karyopherin beta binds stoichiometrically to Ran-GTP and inhibits the Ran GTPase activating protein
    M Floer
    Laboratory of Cell Biology, Howard Hughes Medical Institute, Rockefeller University, New York, New York 10021, USA
    J Biol Chem 271:5313-6. 1996
    ..Ran-GDP bound only weakly to karyopherin beta. We propose that stoichiometric complex formation between karyopherin beta and Ran-GTP renders Ran-GTP inaccessible to RanGAP...
  18. ncbi Targeting Rab GTPases to distinct membrane compartments
    Suzanne Pfeffer
    Department of Biochemistry, Stanford University School of Medicine, Stanford, California 94305 5307, USA
    Nat Rev Mol Cell Biol 5:886-96. 2004
    ..The further discovery of an integral membrane protein that can dissociate prenylated Rab proteins from GDP-dissociation inhibitor gives new insights into the mechanisms of Rab localization...
  19. ncbi Insights into microtubule nucleation from the crystal structure of human gamma-tubulin
    Hector Aldaz
    Howard Hughes Medical Institute and Department of Biochemistry and Biophysics, University of California, San Francisco, 600 16th Street, San Francisco, California 94143, USA
    Nature 435:523-7. 2005
    ..The lateral array of gamma-tubulins we observe in the crystal reveals a unique functional property of a monomeric tubulin...
  20. pmc New insights into how the Rho guanine nucleotide dissociation inhibitor regulates the interaction of Cdc42 with membranes
    Jared L Johnson
    Department of Chemistry, Cornell University, Ithaca, New York 14853, USA
    J Biol Chem 284:23860-71. 2009
    ....
  21. ncbi EF-G-dependent GTP hydrolysis induces translocation accompanied by large conformational changes in the 70S ribosome
    R K Agrawal
    Wadsworth Center, State University of New York at Albany, 12201 0509, USA
    Nat Struct Biol 6:643-7. 1999
    ..Upon GTP hydrolysis, the bifurcation is reversed and an arc-like connection is formed between the base of the stalk and EF-G...
  22. ncbi Peptidyl-tRNA regulates the GTPase activity of translation factors
    Andrey V Zavialov
    Department of Cell and Molecular Biology, BMC, Uppsala University, Box 596, S 75124 Uppsala, Sweden
    Cell 114:113-22. 2003
    ..We also propose a model for translocation of tRNAs in two separate steps, which clarifies the roles of EF-G.GTP and GTP hydrolysis in this process...
  23. ncbi Six GTP-binding proteins of the Era/Obg family are essential for cell growth in Bacillus subtilis
    Takuya Morimoto
    Department of Microbial Cell Biology, Graduate School of Biological Sciences, Nara Institute of Science and Technology, 8916 5, Takayama, Ikoma, Nara 630 0101, Japan
    Microbiology 148:3539-52. 2002
    ..Collectively, these results suggest that members of the GTP-binding Era/Obg family are important proteins with precise, yet still not fully understood, roles in bacterial growth and viability...
  24. pmc The essential GTPase YphC displays a major domain rearrangement associated with nucleotide binding
    Stephen P Muench
    Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield S10 2TN, United Kingdom
    Proc Natl Acad Sci U S A 103:12359-64. 2006
    ....
  25. ncbi TRAPPII subunits are required for the specificity switch of a Ypt-Rab GEF
    Nadya Morozova
    Department of Biological Sciences, Laboratory for Molecular Biology, University of Illinois at Chicago, Molecular Biology Research Building, 900 South Ashland Avenue, Chicago, IL 60607, USA
    Nat Cell Biol 8:1263-9. 2006
    ..Such a 'switchable' GEF could ensure sequential activation of these Ypts, thereby coordinating Golgi entry and exit...
  26. pmc Structural basis for Rab GTPase activation by VPS9 domain exchange factors
    Anna Delprato
    Program in Molecular Medicine and Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Two Biotech, 373 Plantation Street, Worcester, Massachusetts 01605, USA
    Nat Struct Mol Biol 14:406-12. 2007
    ..Autoinhibition can be partially reversed by mutation of conserved residues on the nonpolar face of the predicted amphipathic helix or by assembly of the complex with RABAPTIN-5...
  27. pmc Conserved functions of membrane active GTPases in coated vesicle formation
    Thomas J Pucadyil
    Department of Cell Biology, The Scripps Research Institute TSRI, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Science 325:1217-20. 2009
    ....
  28. ncbi Straight GDP-tubulin protofilaments form in the presence of taxol
    Celine Elie-Caille
    Department of Cellular Machines, BioTechnological Center, University of Technology Dresden, Tatzberg 49, D 01307 Dresden, Germany
    Curr Biol 17:1765-70. 2007
    ..We go on to show that taxol stabilizes microtubules by straightening the GDP protofilament and slowing down the transition of protofilaments from straight to a curved configuration...
  29. ncbi Network analysis of oncogenic Ras activation in cancer
    Edward C Stites
    Beirne B Carter Center for Immunology Research and the Department of Microbiology, University of Virginia, Charlottesville, VA 22908, USA
    Science 318:463-7. 2007
    ..This system-level analysis of the oncogenic Ras network provides new insights and potential therapeutic strategies...
  30. ncbi N-terminal hydrophobic residues of the G-protein ADP-ribosylation factor-1 insert into membrane phospholipids upon GDP to GTP exchange
    B Antonny
    CNRS, Institut de Pharmacologie Moleculaire et Cellulaire, Valbonne, France
    Biochemistry 36:4675-84. 1997
    ..This strongly suggests that, upon GDP/GTP exchange, the N-terminal helix is released from the protein core so its hydrophobic residues can interact with membrane phospholipids...
  31. pmc Cytohesin-1 regulates beta-2 integrin-mediated adhesion through both ARF-GEF function and interaction with LFA-1
    C Geiger
    Laboratorium für Molekulare Biologie, Genzentrum der Universität München, Germany
    EMBO J 19:2525-36. 2000
    ..We therefore propose that both direct regulation of the integrin and concomitant changes in the membrane topology of adherent T cells are modulated by dissectable functions of cytohesin-1...
  32. ncbi Structures of active conformations of Gi alpha 1 and the mechanism of GTP hydrolysis
    D E Coleman
    Howard Hughes Medical Institute, Dallas, TX
    Science 265:1405-12. 1994
    ..The amino-terminal 33 residues are disordered in GTP gamma S-Gi alpha 1, suggesting a mechanism that may promote release of the beta gamma subunit complex when the alpha subunit is activated by GTP...
  33. ncbi Rab27a enables myosin Va-dependent melanosome capture by recruiting the myosin to the organelle
    X Wu
    Laboratory of Cell Biology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Cell Sci 114:1091-100. 2001
    ..These results argue that Rab27a serves as a myosin Va 'receptor', and add to the growing evidence that Rab GTPases regulate vesicle motors as well as SNARE pairing...
  34. ncbi A concerted mechanism for opening the GDP binding pocket and release of the nucleotide in hetero-trimeric G-proteins
    Maxime Louet
    Institut des Biomolecules Max Mousseron IBMM, CNRS UMR5247, Universite Montpellier 1 Universite Montpellier 2, Faculte de Pharmacie, 15 Avenue Charles Flahault, BP 14491, 34093 Montpellier Cedex 05, France
    J Mol Biol 411:298-312. 2011
    ..This model is discussed in the context of the G-protein-coupled receptor/G-protein interaction close to the cell membrane...
  35. ncbi Role of SRP RNA in the GTPase cycles of Ffh and FtsY
    P Peluso
    Howard Hughes Medical Institute and Department of Biochemistry and Biophysics, University of California at San Francisco, 94143 0448, USA
    Biochemistry 40:15224-33. 2001
    ..5S RNA. These results suggest that 4.5S RNA modulates the conformation of the Ffh*FtsY complex and may, in turn, regulate its GTPase activity during the SRP functional cycle...
  36. pmc Interaction of a G protein with an activated receptor opens the interdomain interface in the alpha subunit
    Ned Van Eps
    Jules Stein Eye Institute and Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095 7008, USA
    Proc Natl Acad Sci U S A 108:9420-4. 2011
    ..The interdomain opening is coupled to receptor binding via the C-terminal helix of G(α), the extension of which is a high-affinity receptor binding element...
  37. ncbi A potent and highly selective inhibitor of human alpha-1,3-fucosyltransferase via click chemistry
    Lac V Lee
    Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 Torrey Pines Road, La Jolla, California 92037, USA
    J Am Chem Soc 125:9588-9. 2003
    ....
  38. pmc Carboxyatractyloside effects on brown-fat mitochondria imply that the adenine nucleotide translocator isoforms ANT1 and ANT2 may be responsible for basal and fatty-acid-induced uncoupling respectively
    Irina G Shabalina
    The Wenner Gren Institute, The Arrhenius Laboratories F3, Stockholm University, SE 106 91 Stockholm, Sweden
    Biochem J 399:405-14. 2006
    ..The data are therefore compatible with a tentative model in which the ANT2 isoform mediates fatty-acid-induced uncoupling, whereas the ANT1 isoform may mediate a significant part of the high basal proton leak in brown-fat mitochondria...
  39. ncbi Structural insights into the GTPase domain of Escherichia coli MnmE protein
    Daniel Monleon
    Department of Physical Chemistry, University of Valencia, C Dr Moliner, 50, Burjassot 46100 Valencia, Spain
    Proteins 66:726-39. 2007
    ..Our data support that MnmE, unlike other GTPases, does not use an arginine finger to drive catalysis, although Arg252 may play a role in stabilization of the transition state...
  40. ncbi Binding of allosteric effectors to ribonucleotide reductase protein R1: reduction of active-site cysteines promotes substrate binding
    M Eriksson
    Department of Molecular Biology, Swedish University of Agricultural Sciences, Uppsala Biomedical Center, Sweden
    Structure 5:1077-92. 1997
    ..Our aim has been to crystallographically demonstrate substrate binding and to locate the two effector-binding sites...
  41. pmc eIF5 has GDI activity necessary for translational control by eIF2 phosphorylation
    Martin D Jennings
    Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, UK
    Nature 465:378-81. 2010
    ..Together our studies define a new step in the translation initiation pathway, one that is critical for normal translational controls...
  42. pmc GTPase activation of elongation factor EF-Tu by the ribosome during decoding
    Jan Christian Schuette
    Institut fur Medizinische Physik und Biophysik, Charite Universitatsmedizin Berlin, Berlin, Germany
    EMBO J 28:755-65. 2009
    ..Thus, the structure provides insights into the molecular mechanism of signalling codon recognition from the decoding centre of the 30S subunit to the GTPase centre of EF-Tu...
  43. pmc Mitotic regulator protein RCC1 is complexed with a nuclear ras-related polypeptide
    F R Bischoff
    Project Molecular Biology of Mitosis, Deutsches Krebsforschungszentrum, Heidelberg, Federal Republic of Germany
    Proc Natl Acad Sci U S A 88:10830-4. 1991
    ..We designate this polypeptide Ran, for ras-related nuclear protein...
  44. pmc A novel role for RhoGDI as an inhibitor of GAP proteins
    J F Hancock
    Onyx Pharmaceuticals, Richmond, CA 94806
    EMBO J 12:1915-21. 1993
    ..Thus GDI, by complexing with Rac-GTP and preventing GAP stimulated GTP hydrolysis, may allow transit of the activated form of the Rac protein between physically separated activator and effector proteins in the cell...
  45. ncbi Regulation of Golgi structure and function by ARF-like protein 1 (Arl1)
    L Lu
    Membrane Biology Laboratory, Institute of Molecular and Cell Biology, Singapore
    J Cell Sci 114:4543-55. 2001
    ..On the basis of these observations, we propose that one of the mechanisms for the cell to regulate the structure and function of the Golgi apparatus is through the action of Arl1...
  46. ncbi Two distinct signaling pathways upregulate NMDA receptor responses via two distinct metabotropic glutamate receptor subtypes
    Pascal Benquet
    Brain Research Institute, University of Zurich, CH 8057 Zurich, Switzerland
    J Neurosci 22:9679-86. 2002
    ..These two pathways are likely to contribute significantly to the highly differentiated control of NMDA receptor function...
  47. ncbi The Rac-RhoGDI complex and the structural basis for the regulation of Rho proteins by RhoGDI
    K Scheffzek
    Max Planck Institut fur molekulare Physiologie, Abteilung Strukturelle Biologie, Otto Hahn Str 11, 44227 Dortmund, Germany
    Nat Struct Biol 7:122-6. 2000
    ..The architecture of the complex interface suggests a mechanism for the inhibition of guanine nucleotide dissociation that is based on the stabilization of the magnesium (Mg2+) ion in the nucleotide binding pocket...
  48. pmc A novel switch region regulates H-ras membrane orientation and signal output
    Daniel Abankwa
    Molecular Cell Biology, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia
    EMBO J 27:727-35. 2008
    ..The results illustrate how the plasma membrane spatially constrains signalling conformations by acting as a semi-neutral interaction partner...
  49. ncbi Crystal structure of the ternary complex of Phe-tRNAPhe, EF-Tu, and a GTP analog
    P Nissen
    Department of Biostructural Chemistry, Institute of Chemistry, Aarhus University, Denmark
    Science 270:1464-72. 1995
    ..The overall shape of the ternary complex is similar to that of the translocation factor, EF-G-GDP, and this suggests a novel mechanism involving "molecular mimicry" in the translational apparatus...
  50. ncbi Structure of the G60A mutant of Ras: implications for the dominant negative effect
    Bradley Ford
    Department of Physiology and Biophysics, Stony Brook University, Stony Brook, New York 11794 8661, USA
    J Biol Chem 280:25697-705. 2005
    ..Our data suggest that the dominant negative effect observed for RasG60A.GTP could result from the sequestering of Sos in a non-productive Ras-GTP-guanine nucleotide exchange factor ternary complex...
  51. pmc Kinetics of the interactions between yeast elongation factors 1A and 1Balpha, guanine nucleotides, and aminoacyl-tRNA
    Kirill B Gromadski
    Institute of Physical Biochemistry, University of Witten Herdecke, Stockumer Strasse 10, D 58448 Witten, Germany
    J Biol Chem 282:35629-37. 2007
    ..eEF1A.GTP binds Phe-tRNA(Phe) with a K(d) of 3 nm, whereas eEF1A.GDP shows no significant binding, indicating that eEF1A has similar tRNA binding properties as its prokaryotic homolog, EF-Tu...
  52. pmc Change in nutritional status modulates the abundance of critical pre-initiation intermediate complexes during translation initiation in vivo
    Chingakham Ranjit Singh
    Molecular Cellular and Developmental Biology Program, Division of Biology, Kansas State University, Manhattan, KS 66506, USA
    J Mol Biol 370:315-30. 2007
    ..Interestingly, the TC increase is suppressed by eIF5 overexpression and Gcn2p expression. Thus, eIF2B-catalyzed TC formation appears to be fine-tuned by eIF2 phosphorylation and the novel eIF2/eIF5 complex lacking tRNA(i)(Met)...
  53. pmc Salmonella enterica serovar Typhimurium BipA exhibits two distinct ribosome binding modes
    Megan A deLivron
    University of Connecticut, Dept of Molecular and Cell Biology, Storrs, CT 06250, USA
    J Bacteriol 190:5944-52. 2008
    ..The data show that this differential binding is brought about by the presence of ppGpp, an alarmone that signals the onset of stress-related events in bacteria...
  54. pmc Thermodynamic and kinetic framework of selenocysteyl-tRNASec recognition by elongation factor SelB
    Alena Paleskava
    Department of Physical Biochemistry, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Gottingen, Germany
    J Biol Chem 285:3014-20. 2010
    ..The mode of tRNA recognition by SelB is reminiscent of another specialized factor, eIF2, rather than of EF-Tu, the common delivery factor for all other aminoacyl-tRNAs, in line with a common evolutionary ancestry of SelB and eIF2...
  55. pmc Importin-beta is a GDP-to-GTP exchange factor of Ran: implications for the mechanism of nuclear import
    Thierry G Lonhienne
    Australian Research Council Centre of Excellence for Integrative Legume Research, School of Chemistry and Molecular Biosciences, University of Queensland, QLD 4072, St Lucia, Australia
    J Biol Chem 284:22549-58. 2009
    ..The exchange is also inhibited by nuclear-transport factor-2 (NTF2). We suggest a mechanism for nuclear import, additional to the established RCC1 (Ran-guanine exchange factor)-dependent pathway that incorporates these results...
  56. pmc Conserved bipartite motifs in yeast eIF5 and eIF2Bepsilon, GTPase-activating and GDP-GTP exchange factors in translation initiation, mediate binding to their common substrate eIF2
    K Asano
    Laboratory of Eukaryotic Gene Regulation, National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892, USA
    EMBO J 18:1673-88. 1999
    ..Thus, the bipartite motif in eIF5 appears to be multifunctional, stimulating its recruitment to the 40S pre-initiation complex through interaction with eIF3 in addition to binding of its substrate eIF2...
  57. pmc The membrane protein FeoB contains an intramolecular G protein essential for Fe(II) uptake in bacteria
    Thomas C Marlovits
    Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, P O Box 208024, New Haven, CT 06520 8024, USA
    Proc Natl Acad Sci U S A 99:16243-8. 2002
    ..These findings raise the intriguing question whether FeoB represents a primordial archetype of G protein-regulated membrane proteins...
  58. pmc Mechanochemical model of microtubule structure and self-assembly kinetics
    Vincent VanBuren
    Department of Biological Sciences, Lehigh University, Bethlehem, PA, USA
    Biophys J 89:2911-26. 2005
    ..Finally, simulations of the binding and structural effects of XMAP215 produced the experimentally observed growth and shortening rates, and tip structure...
  59. ncbi The structure of the G protein heterotrimer Gi alpha 1 beta 1 gamma 2
    M A Wall
    Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas 75235, USA
    Cell 83:1047-58. 1995
    ..Repeated WD motifs in beta form a circularized sevenfold beta propeller. The conserved cores of these motifs are a scaffold for display of their more variable linkers on the exterior face of each propeller blade...
  60. pmc Late events of translation initiation in bacteria: a kinetic analysis
    J Tomsic
    Laboratory of Genetics, Department of Biology MCA, University of Camerino, 62032 Camerino MC, Italy
    EMBO J 19:2127-36. 2000
    ..2/s. Omission of GTP or its replacement with GDP had no effect, indicating that neither the adjustment of fMet-tRNA(fMet) in the P site nor the release of IF2 from the ribosome required GTP hydrolysis...
  61. ncbi Structure of the Sec23/24-Sar1 pre-budding complex of the COPII vesicle coat
    Xiping Bi
    Howard Hughes Medical Institute and the Cellular Biochemistry and Biophysics Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10021, USA
    Nature 419:271-7. 2002
    ..These observations establish the structural basis for GTP-dependent recruitment of a vesicular coat complex, and for uncoating through coat-controlled GTP hydrolysis...
  62. ncbi The structure of the Escherichia coli EF-Tu.EF-Ts complex at 2.5 A resolution
    T Kawashima
    European Molecular Biology Laboratory, Grenoble Outstation, France
    Nature 379:511-8. 1996
    ..The interaction of EF-Ts with EF-Tu results principally in the disruption of the Mg2+ ion binding site, thereby reducing the affinity of EF-Tu for guanine nucleotides...
  63. pmc Mapping allosteric connections from the receptor to the nucleotide-binding pocket of heterotrimeric G proteins
    William M Oldham
    Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232 6600, USA
    Proc Natl Acad Sci U S A 104:7927-32. 2007
    ..The data identify a putative pathway of allosteric changes triggered by receptor binding and, together with previously published data, suggest elements of a mechanism for receptor-catalyzed nucleotide exchange...
  64. pmc Release factor RF3 in E.coli accelerates the dissociation of release factors RF1 and RF2 from the ribosome in a GTP-dependent manner
    D V Freistroffer
    Department of Molecular Biology, Uppsala University, BMC, Sweden
    EMBO J 16:4126-33. 1997
    ..A model is proposed which explains how RF3 recycles RF1 and RF2 by displacing the factors from the ribosome after the release of peptide...
  65. ncbi GAIP and RGS4 are GTPase-activating proteins for the Gi subfamily of G protein alpha subunits
    D M Berman
    Department of Pharmacology University of Texas Southwestern Medical Center Dallas 75235, USA
    Cell 86:445-52. 1996
    ..RGS4 activates the GTPase activity of certain Gi alpha 1 mutants (e.g., R178C), but not others (e.g., Q204L). The GAP activity of RGS proteins is consistent with their proposed role as negative regulators of G protein-mediated signaling...
  66. pmc Potassium-activated GTPase reaction in the G Protein-coupled ferrous iron transporter B
    Miriam Rose Ash
    Structural Biology Program, Centenary Institute, Sydney, New South Wales 2042, Australia
    J Biol Chem 285:14594-602. 2010
    ..In addition, the accelerated hydrolysis rate opens up the possibility that FeoB might indeed function as an active transporter...
  67. pmc Structure-based discovery of an inhibitor of Arf activation by Sec7 domains through targeting of protein-protein complexes
    Julien Viaud
    Institut National de la Sante et de la Recherche Medicale, U554, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5048, Centre de Biochimie Structurale, 34090 Montpellier, France
    Proc Natl Acad Sci U S A 104:10370-5. 2007
    ..Our design method shows that flexible regions in protein-protein complexes provide drugable sites with the potential to develop novel tools for investigating and inhibiting signaling pathways...
  68. pmc Two Galpha(i1) rate-modifying mutations act in concert to allow receptor-independent, steady-state measurements of RGS protein activity
    Thomas Zielinski
    BellBrook Labs, Madison, Wisconsin, USA
    J Biomol Screen 14:1195-206. 2009
    ..However, measuring GAP activity is complicated by slow guanosine diphosphate (GDP) release from Galpha and lack of solution phase assays for detecting free GDP in the presence of ..
  69. ncbi Structure of RGS4 bound to AlF4--activated G(i alpha1): stabilization of the transition state for GTP hydrolysis
    J J Tesmer
    Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas 75235, USA
    Cell 89:251-61. 1997
    ..The binding site for RGS4 on G(i alpha1) is also consistent with the activity of RGS proteins as antagonists of G(alpha) effectors...
  70. pmc Identification of domains and residues within the epsilon subunit of eukaryotic translation initiation factor 2B (eIF2Bepsilon) required for guanine nucleotide exchange reveals a novel activation function promoted by eIF2B complex formation
    E Gomez
    Department of Anatomy and Physiology, Medical Sciences Institute, University of Dundee, Dundee, United Kingdom
    Mol Cell Biol 20:3965-76. 2000
    ..This suggests that the N-terminal region of eIF2Bepsilon is an activation domain that responds to eIF2B complex formation...
  71. pmc Conformational changes in dynamin on GTP binding and oligomerization reported by intrinsic and extrinsic fluorescence
    Elena Solomaha
    Department of Neurobiology, Pharmacology and Physiology, University of Chicago, 947 E 58th St, Chicago, IL 60637, USA
    Biochem J 391:601-11. 2005
    ..In addition, energy transfer was observed when oligomerization was promoted in mixtures of IAEDANS.dynamin-2 and 4-(4-dimethylaminophenylazo)benzoic acid-coupled dynamin-2, an effect that was counteracted by GTP but not GDP...
  72. ncbi Guanosine diphosphate exerts a lower effect on superoxide release from mitochondrial matrix in the brains of uncoupling protein-2 knockout mice: new evidence for a putative novel function of uncoupling proteins as superoxide anion transporters
    Jan M Suski
    Department of Biochemistry, Nencki Institute of Experimental Biology, Warsaw, Poland
    Biochem Biophys Res Commun 428:234-8. 2012
    ..This putative novel UCP2 activity, evaluated by the use of UCP2-knockout transgenic animals, along with the known antioxidant defence systems, may provide additional protection from ROS in brain mitochondria...
  73. ncbi A novel binding protein composed of homophilic tetramer exhibits unique properties for the small GTPase Rab5
    Kota Saito
    Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113 0033, Japan
    J Biol Chem 277:3412-8. 2002
    ..Possible roles of the quaternary structure have been discussed in terms of the Rab5-mediated signaling...
  74. ncbi RhoGDI-3 is a new GDP dissociation inhibitor (GDI). Identification of a non-cytosolic GDI protein interacting with the small GTP-binding proteins RhoB and RhoG
    G Zalcman
    Unité INSERM 248, Section de Recherche, Institut Curie, 26 Rue d Ulm, 75231 Paris Cedex 05, France
    J Biol Chem 271:30366-74. 1996
    ..No interaction is found with RhoA, RhoC, or Rac1 proteins. We show that GDI-3 is able to inhibit GDP/GTP exchange of RhoB and to release GDP-bound but not GTP-bound RhoB from cell membranes...
  75. ncbi Elongation factor Ts of Chlamydia trachomatis: structure of the gene and properties of the protein
    Y Zhang
    Maxwell Finland Laboratory for Infectious Diseases, Boston Medical Center, Boston University School of Medicine, Massachusetts 02118, USA
    Arch Biochem Biophys 344:43-52. 1997
    ..coli elongation factor Tu (EF-Tu). These data show that the second gene of the identified cluster is tsf. Unlike EF-Ts from any other species, its activity was comparable to that of E. coli EF-Ts in exchange reaction with E. coli EF-Tu...
  76. ncbi Structural evidence for a common intermediate in small G protein-GEF reactions
    Christoph Thomas
    Max Planck Institute of Molecular Physiology, Otto Hahn Strasse 11, 44227 Dortmund, Germany
    Mol Cell 25:141-9. 2007
    ..The features of the latter complex, a transient intermediate of the exchange reaction never directly observed before, suggest a common mechanism of catalyzed nucleotide exchange applicable to small G proteins in general...
  77. ncbi Crystal structure of the Rac1-RhoGDI complex involved in nadph oxidase activation
    S Grizot
    Institut de Biologie Structurale, CEA CNRS UJF, UMR 5075, 41 rue Jules Horowitz, 38027 Grenoble Cedex 1, France
    Biochemistry 40:10007-13. 2001
    ..In the Rac1-RhoGDI complex, the accessibility of the effector loops of Rac1 probably accounts for the ability of the Rac1-RhoGDI complex to activate the NADPH oxidase...
  78. pmc Helix dipole movement and conformational variability contribute to allosteric GDP release in Galphai subunits
    Anita M Preininger
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee 37232 6600, USA
    Biochemistry 48:2630-42. 2009
    ..Combined with previous evidence in the literature, the structural analysis supports the critical role of electrostatics of the alpha5 helix dipole and overall conformational variability during nucleotide release...
  79. ncbi Analysis of GTPases carrying hydrophobic amino acid substitutions in lieu of the catalytic glutamine: implications for GTP hydrolysis
    Rajeev Mishra
    Bioinformatics Center, School of Information Technology, Jawaharlal Nehru University, New Delhi, India
    Proteins 59:332-8. 2005
    ..This conformation allows us to hypothesize that, unlike in classical GTPases, catalytic residues could be supplied by regions other than the Switch II (i.e., either the insertions or a neighboring domain)...
  80. pmc Ligand interactions with eukaryotic translation initiation factor 2: role of the gamma-subunit
    F L Erickson
    University of Texas at Dallas, Department of Molecular and Cell Biology, Richardson 75083 0688, USA
    EMBO J 15:6311-20. 1996
    ..These studies indicate that the gamma-subunit of eIF-2 does indeed provide EF-Tu-like function to the eIF-2 complex, and further suggest that the level of Met-tRNAi(Met) is critical for maintaining wild-type rates of initiation in vivo...
  81. pmc Nucleotide-dependent bending flexibility of tubulin regulates microtubule assembly
    Hong Wei Wang
    Howard Hughes Medical Institute, University of California Berkeley, Berkeley, California 94720 3200, USA
    Nature 435:911-5. 2005
    ..Closure into a microtubule does not require GTP hydrolysis...
  82. ncbi Gbetagamma inhibits Galpha GTPase-activating proteins by inhibition of Galpha-GTP binding during stimulation by receptor
    Wei Tang
    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9041, USA
    J Biol Chem 281:4746-53. 2006
    ....
  83. ncbi The crystal structure of the small GTPase Rab11b reveals critical differences relative to the Rab11a isoform
    Sandra M N Scapin
    Center for Structural Molecular Biology, Brazilian Synchrotron Light Laboratory, LNLS, P O Box 6192, CEP 13084 971, Campinas, SP, Brazil
    J Struct Biol 154:260-8. 2006
    ..This 3(10)-helix is not found in the Rab11a-GDP structure, which possesses a longer alpha2 helix, spanning from residue 73 to 82 alpha-helix 5...
  84. pmc Drosophila GoLoco-protein Pins is a target of Galpha(o)-mediated G protein-coupled receptor signaling
    Damir Kopein
    Department of Biology, University of Konstanz, D 78457 Konstanz, Germany
    Mol Biol Cell 20:3865-77. 2009
    ..g., in the context of the nervous system development, where Galpha(o) acts downstream from Frizzled and redundantly with Galpha(i) to control the asymmetry of cell divisions...
  85. pmc The pretranslocation ribosome is targeted by GTP-bound EF-G in partially activated form
    Vasili Hauryliuk
    Department of Cell and Molecular Biology, Molecular Biology Program, Uppsala University, S 75 124 Uppsala, Sweden
    Proc Natl Acad Sci U S A 105:15678-83. 2008
    ..We propose that the active overall conformation of EF-G is attained only in complex with the ribosome in its "ratcheted state," with hybrid tRNA binding sites...
  86. ncbi Kinetics of interaction of Rab5 and Rab7 with nucleotides and magnesium ions
    I Simon
    Abteilung Physikalische Biochemie, Max Planck Institut fur molekulare Physiologie, Rheinlanddamm 201, 44139 Dortmund
    J Biol Chem 271:20470-8. 1996
    ..The results demonstrate a high degree of mechanistic similarity between the Rab proteins and other GTP-binding proteins, which have been examined in detail, including Ha-Ras p21, Ran, and EF-Tu...
  87. ncbi Conformational changes in human Arf1 on nucleotide exchange and deletion of membrane-binding elements
    Ronald D Seidel
    Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia 30602 4712, USA
    J Biol Chem 279:48307-18. 2004
    ..Results from NMR experiments presented here on Arf1.GDP and Delta17Arf1.GDP in solution reveal substantial structural differences that can only be associated with N-terminal truncation...
  88. ncbi The structure of rat ADP-ribosylation factor-1 (ARF-1) complexed to GDP determined from two different crystal forms
    S E Greasley
    Glaxo Research and Development, Department of Biomolecular Structure, Stevenage, UK
    Nat Struct Biol 2:797-806. 1995
    ..The dimer interface involves a region of the ARF-1 molecule that is analogous to the effector domain in p21 ras and may mediate interactions with its effectors...
  89. pmc Substrate binding disrupts dimerization and induces nucleotide exchange of the chloroplast GTPase Toc33
    Mislav Oreb
    Center for Membrane Proteomics and the Cluster of Excellence Frankfurt, Department of Biosciences, Molecular Cell Biology of Plants, Goethe University Frankfurt, Max von Laue Str 8, D 60438 Frankfurt am Main, Germany
    Biochem J 436:313-9. 2011
    ..We discuss this novel regulatory mode and its impact on the current models of protein import into the chloroplast...
  90. pmc Structural basis of GDP release and gating in G protein coupled Fe2+ transport
    Amy Guilfoyle
    Centenary Institute, Sydney, New South Wales, Australia
    EMBO J 28:2677-85. 2009
    ..From these results, structural parallels are drawn to eukaryotic G protein coupled membrane processes...
  91. pmc Tubulin dimers oligomerize before their incorporation into microtubules
    Julien Mozziconacci
    Pierre et Marie Curie University, UMR 7600 LPTMC, Paris, France
    PLoS ONE 3:e3821. 2008
    ..Our approach provides a solid experimental framework to better understand the role of MAPs in MT nucleation and growth...
  92. ncbi Functional study on GTP hydrolysis by the GTP-binding protein from Sulfolobus solfataricus, a member of the HflX family
    Bo Huang
    Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101, China
    J Biochem 148:103-13. 2010
    ..Together with functional studies of other mutants, we conclude that the classical view of GTP hydrolysis mechanism likely remains the same in the HflX family with a twist in the entity of the nucleophilic alignment...
  93. pmc Characterization of a novel prokaryotic GDP dissociation inhibitor domain from the G protein coupled membrane protein FeoB
    Edward T Eng
    Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, PO Box 208024, New Haven, CT 06520 8024, USA
    J Mol Biol 375:1086-97. 2008
    ..Our findings suggest that Fe(II) uptake in bacteria involves a G protein regulatory pathway reminiscent of signaling mechanisms found in higher-order organisms...
  94. ncbi Structure and function of the FeoB G-domain from Methanococcus jannaschii
    Stefan Köster
    Department of Structural Biology, Max Planck Institute of Biophysics, Frankfurt am Main, Germany
    J Mol Biol 392:405-19. 2009
    ..Together with the C-terminal helix, this loop may transmit the information about the nucleotide-bound state from the G-domain to the transmembrane region of FeoB...
  95. ncbi Intrinsic bending of microtubule protofilaments
    Andrea Grafmüller
    Department of Chemistry, James Franck Institute, and Computation Institute, University of Chicago, 5735 S Ellis Avenue, Chicago, IL 60637, USA
    Structure 19:409-17. 2011
    ..There are no observable differences between the mesoscopic properties of the contacts in GTP and GDP-bound tubulin or the intradime and interdimer interfaces...
  96. pmc Distinct GDP/GTP bound states of the tandem G-domains of EngA regulate ribosome binding
    Sushil Kumar Tomar
    Department of Biological Sciences and Bioengineering, Indian Institute of Technology, Kanpur 208016, India
    Nucleic Acids Res 37:2359-70. 2009
    ..Our results suggest a model where distinct nucleotide-bound states of the two G-domains regulate formation of specific EngA-ribosome complexes...
  97. ncbi Bacterial expression and one-step purification of an isotope-labeled heterotrimeric G-protein alpha-subunit
    Najmoutin G Abdulaev
    Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, Rockville, MD 20850, USA
    J Biomol NMR 32:31-40. 2005
    ..Comparisons of the 15N-HSQC spectra reveals a number of changes in chemical shifts of the 1HN, 15N crosspeaks that are discussed with respect to expected changes in the protein conformation associated with G(alpha) activation...
  98. ncbi Helix unwinding in the effector region of elongation factor EF-Tu-GDP
    G Polekhina
    Institute of Molecular and Structural Biology, Aarhus University, Langelandsgade, Denmark
    Structure 4:1141-51. 1996
    ..The aim of this work was to establish the overall structure of intact EF-Tu-GDP, in particular the structure of the effector domain...
  99. ncbi Kap95p binding induces the switch loops of RanGDP to adopt the GTP-bound conformation: implications for nuclear import complex assembly dynamics
    Jade K Forwood
    School of Biomedical Sciences, Charles Sturt University, Wagga Wagga 2650, Australia
    J Mol Biol 383:772-82. 2008
    ..The structure of the complex provides insights into the structural basis for the gradation of affinities regulating nuclear protein transport...
  100. ncbi The GDP/GTP cycle of Rab5 in the regulation of endocytotic membrane traffic
    G Vitale
    Cell Biology Programme, European Molecular Biology Laboratory, Heidelberg, Germany
    Cold Spring Harb Symp Quant Biol 60:211-20. 1995
  101. ncbi An intramolecular contact in Galpha transducin that participates in maintaining its intrinsic GDP release rate
    T O Thomas
    Institute for Neuroscience, Northwestern University, Chicago, Illinois, USA
    Mol Cell Biol Res Commun 4:282-91. 2001
    ..Similarly, introduction of this contact in wild-type Galpha(i1) decreased the GDP release rate of Galpha(i1) by half. Differences in GDP release rates may reflect physiological roles these proteins play in living systems...

Research Grants47

  1. Mechanism of G protein Activation by Ric-8A
    Stephen R Sprang; Fiscal Year: 2013
    ..Ric-8A is a Guanine nucleotide Exchange Factor (GEF) that catalyzes the exchange of guanosine diphosphate (GDP) for guanosine triphosphate (GTP) at the active site of G?...
  2. NEUROFIBROMATOSIS TYPE 1 GENE REGULATES MYELOPOIESIS
    DAVID CLAPP; Fiscal Year: 2001
    ..and differentiation by cycling between an active guanosine triphosphate (GTP)-bound state and an inactive guanosine diphosphate (GDP)-bound state...
  3. KINETICS AND CHEMISTRY OF ALLOSTERIC INTERACTIONS
    Thomas Smith; Fiscal Year: 1992
    ..Kinetics, NMR, gene cloning, and protein modification and structural analyses are among the techniques to be used...
  4. STRUCTURAL BASIS FOR BINDING TO G PROTEIN BETA GAMMA
    Alan Smrcka; Fiscal Year: 2007
    ..4. Identification of sites of interaction G protein betagamma subunits with cellular targets using deuterium exchange mass spectrometry. ..
  5. REGULATION OF SUPEROXIDE PRODUCTION BY HUMAN NEUTROPHILS
    Jeffrey Friedman; Fiscal Year: 2007
    ..These studies may ultimately lead to new pharmacological methods for controlling oxygen radical-mediated tissue damage as well as an improved understanding of the pathophysiology of CGD. ..
  6. Novel Pathways of Polyphosphate Synthesis
    Arthur Kornberg; Fiscal Year: 2005
    ..abstract_text> ..
  7. Southeast Collaboratory for High-Field Biomolecular NMR
    James Prestegard; Fiscal Year: 2006
    ..Target areas for future expansion include carbohydrates and metallo-proteins. ..
  8. RECEPTOR COUPLING TO G12 AND G13
    David Manning; Fiscal Year: 2006
    ..abstract_text> ..
  9. Mechanisms of Nucleotide Release by Airway Epithelia
    Eduardo Lazarowski; Fiscal Year: 2006
    ..Delineation of nucleotide-releasing mechanisms will provide new possibilities to improve MCC function in chronic lung diseases characterized by mucin-obstructed and inflamed airways. [unreadable] [unreadable]..
  10. Reactive Oxygen Species in Anti-Viral Airway Host Defense
    Jeffrey Friedman; Fiscal Year: 2008
    ..Our studies will show if oxidases are a promising target for therapeutic drug development. [unreadable] [unreadable] [unreadable] [unreadable]..
  11. NMR INVESTIGATIONS OF CELL SURFACE OLIGOSACCHARIDES
    James Prestegard; Fiscal Year: 2008
    ..Abnormal function of both systems relate to current health concerns. ..
  12. INTRACELLULAR TRANSPORT--THE MANNOSE-PHOSPHATE RECEPTOR
    Suzanne Pfeffer; Fiscal Year: 2008
    ..These studies have important implications for our understanding of growth control and antigen processing, and will provide fundamental information regarding the mechanism of receptor trafficking in mammalian cells. ..
  13. Properties of Ion Channels that Control Secretion
    JOHN ENYEART; Fiscal Year: 2008
    ..abstract_text> ..
  14. hGBP-1 in the inhibition of cell growth by IFNs
    DEBORAH VESTAL; Fiscal Year: 2007
    ..Understanding how hGBP-1 functions would make a significant IFNs inhibit cell growth. ..
  15. Mechanisms of Calcium Transients in Neuronal Development
    Nicholas Spitzer; Fiscal Year: 2009
    ..The long term goal is to provide information about the cellular and molecular machinery that governs processes of development, which will contribute to understanding developmental disorders of the nervous system. ..
  16. Mechanotransduction in Fibroblast
    Diane L Barber; Fiscal Year: 2010
    ....
  17. Ras, Cycling and Inhibition.
    Nicolas Nassar; Fiscal Year: 2010
    ..The outcome of the proposed research should improve our understanding of the regulation of key signaling proteins and our ability to interfere with their action in human diseases. ..
  18. Molecular Analysis of the CCC185 Golgin
    Suzanne R Pfeffer; Fiscal Year: 2010
    ..This work has broad implications for our understanding of vesicle docking and fusion events within the secretory and endocytic pathways that are essential for normal human health and disease. ..
  19. Engagement of heterotrimeric G proteins by Sonic hedgehog
    DAVID RANDELL MANNING; Fiscal Year: 2010
    ..An understanding of the mechanisms by which Sonic hedgehog signals will provide important leads into how that signaling might be manipulated in a therapeutic context. ..
  20. GPCR signaling complexes in living cells
    NEVIN ALAN LAMBERT; Fiscal Year: 2010
    ..g. when and where receptors, G-proteins and effector molecules interact with each other to transmit signals. The goal of this project is to provide this information. ..
  21. REGULATION OF HUMAN PHAGOCYTE FUNCTION BY RAC PROTEINS
    Ulla Knaus; Fiscal Year: 2006
    ..These studies will yield novel insights into the overall control of oxidant formation by innate immune cells. ..
  22. RhoH GTPase in blood cell and cancer development
    Yi Gu; Fiscal Year: 2006
    ..Given the lineage-restricted expression of RhoH such an observation could have important therapeutic implication. ..
  23. Frontiers of NMR in Molecular Biology VIII
    James Prestegard; Fiscal Year: 2003
    ..Discussion of more practical aspects will be promoted by the organization of afternoon workshops having a less formal structure. ..
  24. ATP P2X RECEPTORS AND NOCICEPTIVE TRANSMISSION
    Jianguo Gu; Fiscal Year: 2002
    ..The long-term objective of our studies are to explore the roles of P2x receptors in both centrally generated pathological pain and in sensory hypersensitivity such as hyperalgesia. ..
  25. PLATELET DERIVED GROWTH FACTOR IN FOLLICLE DEVELOPMENT
    Christopher Taylor; Fiscal Year: 2002
    ..abstract_text> ..
  26. MECHANISM OF VISUAL EXCITATION
    Thomas Ebrey; Fiscal Year: 2002
    ....
  27. SIGNAL TRANDUCTION IN CELL PROLIFERATION
    David Manning; Fiscal Year: 2002
    ..We will also identify genes activated by LPA and S1P, and the subset whose activation is dependent on NF-kappaB. ..
  28. SIGNALING MECHANISMS OF SOMATOSTATIN RECEPTORS
    DIANE BARBER; Fiscal Year: 2002
    ....
  29. STRUCTURE/FUNCTION OF YEAST TRANSLATION FACTOR EIF4G
    Alan Sachs; Fiscal Year: 2001
    ....
  30. ROLE OF PROTEIN PHOSPHATASES IN INSULIN SECRETION
    Anjaneyulu Kowluru; Fiscal Year: 2004
    ....
  31. MECHANISM OF INITIATION OF PROTEIN BIOSYNTHESIS
    JOHN HERSHEY; Fiscal Year: 2004
    ..The experiments will help elucidate the function and regulation of these key initiation factors. ..
  32. MOLECULAR MECHANISMS CONTROLLING BACTERIORHODOPSIN
    Thomas Ebrey; Fiscal Year: 2004
    ....
  33. Biochemical Mechanisms of Polyphosphate in Metabolism
    Arthur Kornberg; Fiscal Year: 2005
    ..In view of the ubiquity of poly P in animal cells and subcellular organelles (particularly nuclei), it seems likely that poly P serves multiple functions in human metabolism that affect growth, differentiation and disease. ..
  34. PKC modulation of calcium current and anesthetic action
    GANESAN KAMATCHI; Fiscal Year: 2007
    ..abstract_text> ..
  35. Regulation of G-protein signaling in CNS neurons
    Nevin Lambert; Fiscal Year: 2006
    ..If our hypothesis is correct, we will identify presynaptic terminals as key sites for the adaptive changes responsible for the development of drug effects, drug tolerance and drug dependence. ..
  36. Protein Prenyltransferases in Glucose-Stimulated Insulin Secretion
    Anjaneyulu Kowluru; Fiscal Year: 2010
    ....
  37. Cell Type and Stimulus-Specific Signaling Role of CDC42 in Blood
    Yi Zheng; Fiscal Year: 2010
    ..abstract_text> ..
  38. NBCe1 and n1: Crystal Structure Determination
    HARRY GILL; Fiscal Year: 2007
    ..The proposed study will provide key insights on the molecular mechanisms of renal HCO3- transport and will enhance our understanding of processes fundamental to renal disease. [unreadable] [unreadable] [unreadable]..
  39. CALCIUM AND ENDOCYTOTIC MEMBRANE RETRIEVAL
    Nevin Lambert; Fiscal Year: 2003
    ..Specifically we will determine how exocytotic activity influences membrane depolarization and the cellular distribution of P-type calcium channels. ..
  40. THERMODYNAMICS OF BIOCHEMICAL SYSTEMS
    ROBERT ALBERTY; Fiscal Year: 2005
    ..This quantitative treatment of the literature data on biochemical reactions will uncover errors because deltafG'0 values can be determined by use of two or more biochemical reactions, which should give the same answer. ..
  41. MECHANISMS OF MICROTUBULE AND MITOTIC SPINDLE ASSEMBLY
    Lynne Cassimeris; Fiscal Year: 2006
    ..To address these issues, we will apply a number of fluorescence-based imaging methods combined with siRNA or injection of function-blocking proteins or antibodies. ..
  42. Renal Epithelial Sodium Channels and Syntaxins
    Sunil Saxena; Fiscal Year: 2006
    ..Epitope mapping will be used to optimize the specificity of polyclonal antibodies, and anti-sense oligonucleotides will be used to modulate the level of endogenous proteins in the mpkCCDC14 line. ..
  43. Nano-HPLC-ESI Quadrupole Ion Trap Mass Spectrometer
    Alan Smrcka; Fiscal Year: 2005
    ..A cost recovery plan will be implemented that will cover costs in future years. ..
  44. ORGANIZATION OF APICAL CELL JUNCTIONS IN EYE
    Kwang Wook Choi; Fiscal Year: 2005
    ..Therefore, studies on novel interaction of Crb and Par complexes will provide important insights into the mechanism of human CRB 1 in normal retinal development and diseases associated with CRB1 mutations. ..
  45. LOCALIZATION OF THE GOLGI COMPLEX
    Suzanne Pfeffer; Fiscal Year: 2001
    ....
  46. Inhibitory AT2 Receptor:Activation/Signaling Mechanisms
    Ying Hong Feng; Fiscal Year: 2005
    ..This proposal has the potential to open up novel avenues for therapy of hypertrophy and fibrosis. ..