Mechanical force generation by G proteins.
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.
Kosztin
Ioan
I
Department of Physics and Astronomy, University of Missouri, Columbia, MO 65211, USA. kosztini@missouri.edu
Bruinsma
Robijn
R
O'Lague
Paul
P
Schulten
Klaus
K
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
D020409:Molecular Motor Proteins; D006153:Guanosine Diphosphate; D006160:Guanosine Triphosphate; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)