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Elife. 2014 Nov 21;3:e04686. doi: 10.7554/eLife.04686.

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

Author information

1
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, United States.
2
Department of Biology, Brandeis University, Waltham, United States.
3
Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, United States.
4
Department of Molecular and Cellular Biochemistry, Indiana University, Bloomington, United States.

Abstract

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.

KEYWORDS:

biophysics; cryo-EM; human; kinesin; molecular motors; myosin; structural biology

PMID:
25415053
PMCID:
PMC4383081
DOI:
10.7554/eLife.04686
[Indexed for MEDLINE]
Free PMC Article

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