KIF14 binds tightly to microtubules and adopts a rigor-like conformation

J Mol Biol. 2014 Aug 26;426(17):2997-3015. doi: 10.1016/j.jmb.2014.05.030. Epub 2014 Jun 17.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Diphosphate / chemistry
  • Adenosine Triphosphatases / chemistry
  • Amino Acid Sequence
  • Animals
  • Catalytic Domain
  • Crystallography, X-Ray
  • Kinesin / chemistry*
  • Kinetics
  • Mice
  • Microtubules / chemistry*
  • Microtubules / ultrastructure
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Binding
  • Protein Multimerization
  • Protein Stability
  • Protein Structure, Secondary

Substances

  • Adenosine Diphosphate
  • Adenosine Triphosphatases
  • Kif14 protein, mouse
  • Kinesin

Associated data

  • PDB/4OZQ