Force generation in kinesin hinges on cover-neck bundle formation.
In kinesin motors, a fundamental question concerns the mechanism by which ATP binding generates the force required for walking. Analysis of available structures combined with molecular dynamics simulations demonstrates that the conformational change of the neck linker involves the nine-residue-long N-terminal region, the cover strand, as an element that is essential for force generation. Upon ATP binding, it forms a beta sheet with the neck linker, the cover-neck bundle, which induces the forward motion of the neck linker, followed by a latch-type binding to the motor head. The estimated stall force and anisotropic response to external loads calculated from the model agree with force-clamp measurements. The proposed mechanism for force generation by the cover-neck bundle formation appears to apply to several kinesin families. It also elucidates the design principle of kinesin as the smallest known processive motor.
Hwang
Wonmuk
W
Department of Biomedical Engineering, Texas A&M University, College Station, TX 77843, USA. hwm@tamu.edu
Lang
Matthew J
MJ
Karplus
Martin
M
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D003198:Computer Simulation; D006801:Humans; D016547:Kinesins / Q000737:chemistry* / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D008958:Models, Molecular; D011487:Protein Conformation; D013314:Stress, Mechanical
D000255:Adenosine Triphosphate; D016547:Kinesins