title: Mechanical force generation by G proteins.
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.
authors.affiliation: Department of Physics and Astronomy, University of Missouri, Columbia, MO 65211, USA. kosztini@missouri.edu
authors.forename: Ioan
authors.initials: I
authors.lastname: Kosztin
authors.forename: Robijn
authors.initials: R
authors.lastname: Bruinsma
authors.forename: Paul
authors.initials: P
authors.lastname: O'Lague
authors.forename: Klaus
authors.initials: K
authors.lastname: Schulten
mesh_terms: D003198:Computer Simulation; D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D007700:Kinetics; D008958:Models, Molecular; D020409:Molecular Motor Proteins / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D016283:Proto-Oncogene Proteins p21(ras) / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D020409:Molecular Motor Proteins; D006153:Guanosine Diphosphate; D006160:Guanosine Triphosphate; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)