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

eLife

Chen Xu¹  Kaifeng Zhou²  Zhiguo Shang²  Charles V Sindelar²  Jared C Cochran³  Roseann Csencsits⁴ 

[1] Department of Biology, Brandeis University, Waltham, United States;Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, United States;Department of Molecular and Cellular Biochemistry, Indiana University, Bloomington, United States;Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, United States;

关键词: cryo-EM;    molecular motor;    kinesin;    myosin;   

DOI  :  10.7554/eLife.04686

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown