TY - JOUR TI - High-resolution structures of kinesin on microtubules provide a basis for nucleotide-gated force-generation AU - Shang, Zhiguo AU - Zhou, Kaifeng AU - Xu, Chen AU - Csencsits, Roseann AU - Cochran, Jared C AU - Sindelar, Charles V A2 - Hyman, Anthony A VL - 3 PY - 2014 DA - 2014/11/21 SP - e04686 C1 - eLife 2014;3:e04686 DO - 10.7554/eLife.04686 UR - https://doi.org/10.7554/eLife.04686 AB - 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. KW - cryo-EM KW - molecular motor KW - kinesin KW - myosin JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -