Literature DB >> 11904419

Mechanical force generation by G proteins.

Ioan Kosztin1, Robijn Bruinsma, Paul O'Lague, Klaus Schulten.   

Abstract

GTP-hydrolyzing G proteins are molecular switches that play a critical role in cell signaling processes. Here we use molecular dynamics simulations to show that Ras, a monomeric G protein, can generate mechanical force upon hydrolysis. The generated force levels are comparable to those produced by ATP-hydrolyzing motor proteins, consistent with the structural similarities of the catalytic region of motor proteins and G proteins. The force transduction mechanism is based on an irreversible structural change, produced by the hydrolysis, which triggers thermal switching between force-generating substates through changes in the configurational space of the protein.

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Year:  2002        PMID: 11904419      PMCID: PMC122565          DOI: 10.1073/pnas.052209199

Source DB:  PubMed          Journal:  Proc Natl Acad Sci U S A        ISSN: 0027-8424            Impact factor:   11.205


  17 in total

1.  Reversible block of the calcium release channel/ryanodine receptor by protamine, a heparin antidote.

Authors:  P Koulen; B E Ehrlich
Journal:  Mol Biol Cell       Date:  2000-07       Impact factor: 4.138

2.  Calculation of pathways for the conformational transition between the GTP- and GDP-bound states of the Ha-ras-p21 protein: calculations with explicit solvent simulations and comparison with calculations in vacuum.

Authors:  J F Diaz; B Wroblowski; J Schlitter; Y Engelborghs
Journal:  Proteins       Date:  1997-07

3.  Molecular switch in signal transduction: reaction paths of the conformational changes in ras p21.

Authors:  J Ma; M Karplus
Journal:  Proc Natl Acad Sci U S A       Date:  1997-10-28       Impact factor: 11.205

4.  Crystal structures at 2.2 A resolution of the catalytic domains of normal ras protein and an oncogenic mutant complexed with GDP.

Authors:  L A Tong; A M de Vos; M V Milburn; S H Kim
Journal:  J Mol Biol       Date:  1991-02-05       Impact factor: 5.469

5.  Transcription against an applied force.

Authors:  H Yin; M D Wang; K Svoboda; R Landick; S M Block; J Gelles
Journal:  Science       Date:  1995-12-08       Impact factor: 47.728

6.  Comparison of ras-p21 bound to GDP and GTP: differences in protein and ligand dynamics.

Authors:  L V Mello; D M van Aalten; J B Findlay
Journal:  Protein Eng       Date:  1997-04

7.  The Ras-RasGAP complex: structural basis for GTPase activation and its loss in oncogenic Ras mutants.

Authors:  K Scheffzek; M R Ahmadian; W Kabsch; L Wiesmüller; A Lautwein; F Schmitz; A Wittinghofer
Journal:  Science       Date:  1997-07-18       Impact factor: 47.728

Review 8.  G protein mechanisms: insights from structural analysis.

Authors:  S R Sprang
Journal:  Annu Rev Biochem       Date:  1997       Impact factor: 23.643

9.  Solution structure and dynamics of ras p21.GDP determined by heteronuclear three- and four-dimensional NMR spectroscopy.

Authors:  P J Kraulis; P J Domaille; S L Campbell-Burk; T Van Aken; E D Laue
Journal:  Biochemistry       Date:  1994-03-29       Impact factor: 3.162

10.  Refined crystal structure of the triphosphate conformation of H-ras p21 at 1.35 A resolution: implications for the mechanism of GTP hydrolysis.

Authors:  E F Pai; U Krengel; G A Petsko; R S Goody; W Kabsch; A Wittinghofer
Journal:  EMBO J       Date:  1990-08       Impact factor: 11.598

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  12 in total

1.  Relation between the conformational heterogeneity and reaction cycle of Ras: molecular simulation of Ras.

Authors:  Chigusa Kobayashi; Shinji Saito
Journal:  Biophys J       Date:  2010-12-01       Impact factor: 4.033

2.  Through the channel and around the channel: Validating and comparing microscopic approaches for the evaluation of free energy profiles for ion penetration through ion channels.

Authors:  Mitsunori Kato; Arieh Warshel
Journal:  J Phys Chem B       Date:  2005-10-20       Impact factor: 2.991

3.  Dynamic switching mechanisms in LOV1 and LOV2 domains of plant phototropins.

Authors:  Peter L Freddolino; Markus Dittrich; Klaus Schulten
Journal:  Biophys J       Date:  2006-08-25       Impact factor: 4.033

4.  Dynamics of Recognition between tRNA and elongation factor Tu.

Authors:  John Eargle; Alexis A Black; Anurag Sethi; Leonardo G Trabuco; Zaida Luthey-Schulten
Journal:  J Mol Biol       Date:  2008-02-04       Impact factor: 5.469

Review 5.  The mechanobiology of brain function.

Authors:  William J Tyler
Journal:  Nat Rev Neurosci       Date:  2012-12       Impact factor: 34.870

6.  Probing the wild-type HRas activation mechanism using steered molecular dynamics, understanding the energy barrier and role of water in the activation.

Authors:  Neeru Sharma; Uddhavesh Sonavane; Rajendra Joshi
Journal:  Eur Biophys J       Date:  2014-01-20       Impact factor: 1.733

Review 7.  Lessons from computer simulations of Ras proteins in solution and in membrane.

Authors:  Priyanka Prakash; Alemayehu A Gorfe
Journal:  Biochim Biophys Acta       Date:  2013-07-30

8.  Genome-based expression profiles as a single standardized microarray platform for the diagnosis of bladder pain syndrome/interstitial cystitis: an array of 139 genes model.

Authors:  Ling-Hong Tseng; Ilene Chen; Ming-Yang Chen; Chyi-Long Lee; Yi-Hao Lin; L Keith Lloyd
Journal:  Int Urogynecol J Pelvic Floor Dysfunct       Date:  2009-02-13

9.  A fluorescence energy transfer-based mechanical stress sensor for specific proteins in situ.

Authors:  Fanjie Meng; Thomas M Suchyna; Frederick Sachs
Journal:  FEBS J       Date:  2008-05-10       Impact factor: 5.542

10.  Ras and GTPase-activating protein (GAP) drive GTP into a precatalytic state as revealed by combining FTIR and biomolecular simulations.

Authors:  Till Rudack; Fei Xia; Jürgen Schlitter; Carsten Kötting; Klaus Gerwert
Journal:  Proc Natl Acad Sci U S A       Date:  2012-09-04       Impact factor: 11.205

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