The intrinsic load-resisting capacity of kinesin.
Conventional kinesin is a homodimeric motor protein that is capable of walking unidirectionally along a cytoskeletal filament. While previous experiments indicated unyielding unidirectionality against an opposing load up to the so-called stall force, recent experiments also observed limited processive backwalking under superstall loads. This theoretical study seeks to elucidate the molecular mechanical basis for kinesin's steps over the full range of external loads that can possibly be applied to the dimer. We found that kinesin's load-resisting capacity is largely determined by a synergic ratchet-and-pawl mechanism inherent in the dimer. Load susceptibility of this inner molecular mechanical mechanism underlies kinesin's response to various levels of external loads. Computational implementation of the mechanism enabled us to rationalize major trends observed experimentally in kinesin's stalemate and consecutive back steps. The study also predicts several distinct features of kinesin's load-affected motility, which are seemingly counterintuitive but readily verifiable by future experiment.
Institute of Modern Physics, Fudan University, Shanghai 200433, People's Republic of China.
Wenwei
W
Zheng
Dagong
D
Fan
Min
M
Feng
Zhisong
Z
Wang
D000255:Adenosine Triphosphate / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D019295:Computational Biology / Q000379:methods*; D019281:Dimerization; D016547:Kinesins / Q000737:chemistry*; D007700:Kinetics
D000255:Adenosine Triphosphate; D016547:Kinesins