Key result
Cryo-EM reconstructions of the kinesin motor domain reveal mechanisms for nucleotide-gated force generation and stepping.
Why the study?
The mechanistic basis of nucleotide-gated force generation by kinesin motors on microtubules was not fully understood at atomic resolution.
Provides structural insights into the nucleotide-exchange steps and force-generation mechanism of kinesin motors on microtubules.
Answers are grounded in this paper and cite their sources.
Mechanistic scheme for kinesin motility inferred from cryo-EM models; extends prior X-ray structures but leaves open in vivo validation.
Microtubule-based transport by the kinesin motors, powered by ATP hydrolysis, is essential for a wide range of vital processes in eukaryotes. We obtained insight into this process by developing atomic models for no-nucleotide and ATP states of the monomeric kinesin motor domain on microtubules from cryo-EM reconstructions at 5-6 Å resolution. By comparing these models with existing X-ray structures of ADP-bound kinesin, we infer a mechanistic scheme in which microtubule attachment, mediated by a universally conserved 'linchpin' residue in kinesin (N255), triggers a clamshell opening of the nucleotide cleft and accompanying release of ADP. Binding of ATP re-closes the cleft in a manner that tightly couples to translocation of cargo, via kinesin's 'neck linker' element. These structural transitions are reminiscent of the analogous nucleotide-exchange steps in the myosin and F1-ATPase motors and inform how the two heads of a kinesin dimer 'gate' each other to promote coordinated stepping along microtubules.
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Shang et al. (2014) studied this question. Cryo-EM reconstructions of the kinesin motor domain on microtubules at 5-6 Å resolution reveal a mechanistic scheme for nucleotide-gated force-generation and coordinated stepping.
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