Insight into the molecular mechanism of the multitasking kinesin-8 motor

EMBO J. 2010 Oct 20;29(20):3437-47. doi: 10.1038/emboj.2010.220. Epub 2010 Sep 3.


Members of the kinesin-8 motor class have the remarkable ability to both walk towards microtubule plus-ends and depolymerise these ends on arrival, thereby regulating microtubule length. To analyse how kinesin-8 multitasks, we studied the structure and function of the kinesin-8 motor domain. We determined the first crystal structure of a kinesin-8 and used cryo-electron microscopy to calculate the structure of the microtubule-bound motor. Microtubule-bound kinesin-8 reveals a new conformation compared with the crystal structure, including a bent conformation of the α4 relay helix and ordering of functionally important loops. The kinesin-8 motor domain does not depolymerise stabilised microtubules with ATP but does form tubulin rings in the presence of a non-hydrolysable ATP analogue. This shows that, by collaborating, kinesin-8 motor domain molecules can release tubulin from microtubules, and that they have a similar mechanical effect on microtubule ends as kinesin-13, which enables depolymerisation. Our data reveal aspects of the molecular mechanism of kinesin-8 motors that contribute to their unique dual motile and depolymerising functions, which are adapted to control microtubule length.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Cryoelectron Microscopy
  • Crystallography, X-Ray
  • Humans
  • Kinesins / chemistry*
  • Kinesins / genetics
  • Kinesins / metabolism*
  • Microtubules / metabolism
  • Models, Molecular
  • Protein Binding
  • Protein Structure, Secondary*
  • Protein Structure, Tertiary*


  • Adenosine Triphosphate
  • Kinesins

Associated data

  • PDB/3LRE