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High-resolution structures of kinesin on microtubules provide a basis for nucleotide-gated force-generation

2014; eLife Sciences Publications Ltd; Volume: 3; Linguagem: Inglês

10.7554/elife.04686

2050-084X

Zhiguo Shang, Kaifeng Zhou, Xu Chen, R. Csencsits, Jared C. Cochran, Charles V. Sindelar,

Cardiomyopathy and Myosin Studies

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.