@article{9399ca7cb7844013a808218f72f62202,
title = "KIF14 binds tightly to microtubules and adopts a rigor-like conformation",
abstract = "The mitotic kinesin motor protein KIF14 is essential for cytokinesis during cell division and has been implicated in cerebral development and a variety of human cancers. Here we show that the mouse KIF14 motor domain binds tightly to microtubules and does not display typical nucleotide-dependent changes in this affinity. It also has robust ATPase activity but very slow motility. A crystal structure of the ADP-bound form of the KIF14 motor domain reveals a dramatically opened ATP-binding pocket, as if ready to exchange its bound ADP for Mg·ATP. In this state, the central β-sheet is twisted ~ 10° beyond the maximal amount observed in other kinesins. This configuration has only been seen in the nucleotide-free states of myosins - known as the {"}rigor-like{"} state. Fitting of this atomic model to electron density maps from cryo-electron microscopy indicates a distinct binding configuration of the motor domain to microtubules. We postulate that these properties of KIF14 are well suited for stabilizing midbody microtubules during cytokinesis.",
keywords = "KIF14, crystal structure, kinesin, microtubules, motor protein",
author = "Kritica Arora and Lama Talje and Asenjo, {Ana B.} and Parker Andersen and Kaleem Atchia and Monika Joshi and Hernando Sosa and Allingham, {John S.} and Kwok, {Benjamin H.}",
note = "Funding Information: We thank Shuaiqi Guo and Qilu Ye for assistance with diffraction data collection and processing and the AECOM Analytical Imaging Facility for help with EM. This work was supported by funding from the Natural Sciences and Engineering Research Council of Canada (K.A.: Natural Sciences and Engineering Research Council of Canada Postgraduate Scholarships), the Canadian Institutes of Health Research (J.S.A.: MOP-97832 ; B.H.K.: MOP-97928 ), the Ontario Early Researcher Award program (to J.S.A.), and the USA National Institutes of Health (H.S.: National Institutes of Health grant R01-GM083338 ). J.S.A. holds a Canada Research Chair (Tier 2) in Structural Biology. B.H.K. is a recipient of the Fonds de Recherche du Qu{\'e}bec–Sant{\'e} Chercheure-Boursi{\`e}re Junior 1 Award and the Canadian Institutes of Health Research New Investigator Award. B.H.K. acknowledges the support of The Institute for Research in Immunology and Cancer and IRICoR, which are supported in part by the Canadian Center of Excellence in Commercialization and Research, the Canada Foundation for Innovation, and the Fonds de Recherche du Qu{\'e}bec–Sant{\'e}. ",
year = "2014",
month = aug,
day = "26",
doi = "10.1016/j.jmb.2014.05.030",
language = "English (US)",
volume = "426",
pages = "2997--3015",
journal = "Journal of Molecular Biology",
issn = "0022-2836",
publisher = "Academic Press Inc.",
number = "17",
}
