KIF14 Binds Tightly to Microtubules and Adopts a Rigor-Like Conformation

JOURNAL OF MOLECULAR BIOLOGY

卷:426

Article

Arora, Kritica¹  Talje, Lama²  Asenjo, Ana B.³  Andersen, Parker²  Atchia, Kaleem²  Joshi, Monika¹  Sosa, Hernando³  Allingham, John S.¹  Kwok, Benjamin H.² 

[1] Queens Univ, Dept Biomed & Mol Sci, Kingston, ON K7L 3N6, Canada

[2] Univ Montreal, Inst Res lmmunol & Canc, Dept Med, Montreal, PQ H3C 3J7, Canada

[3] Albert Einstein Coll Med, Dept Physiol & Biophys, Bronx, NY 10461 USA

关键词: kinesin;    KIF14;    motor protein;    microtubules;    crystal structure;   

DOI  :  10.1016/j.jmb.2014.05.030

来源: Elsevier

【 摘 要 】

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 center dot ATP. In this state, the central beta-sheet is twisted similar to 10 degrees 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. (C) 2014 The Authors. Published by Elsevier Ltd.

【 授权许可】

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