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.
Original language | English (US) |
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Pages (from-to) | 2997-3015 |
Number of pages | 19 |
Journal | Journal of Molecular Biology |
Volume | 426 |
Issue number | 17 |
DOIs | |
State | Published - Aug 26 2014 |
Keywords
- KIF14
- crystal structure
- kinesin
- microtubules
- motor protein
ASJC Scopus subject areas
- Structural Biology
- Molecular Biology