Insight into the molecular mechanism of the multitasking kinesin-8 motor
Peters, Carsten and Brejc, K. and Belmont, L. and Bodey, Andrew J. and Lee, Y. and Yu, M. and Guo, J. and Sakowicz, R. and Hartman, J. and Moores, Carolyn A. (2010) Insight into the molecular mechanism of the multitasking kinesin-8 motor. The EMBO Journal 29 (20), pp. 3437-3447. ISSN 0261-4189.
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.
|Keyword(s) / Subject(s):||cryo-electron microscopy, crystallography, cytoskeleton regulation, kinesin, microtubule|
|School:||Birkbeck Schools and Departments > School of Science > Biological Sciences|
|Research Centre:||Structural Molecular Biology, Institute of (ISMB)|
|Date Deposited:||05 Apr 2011 14:01|
|Last Modified:||06 Dec 2016 11:12|
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