| Structural highlights
Function
[KI18A_HUMAN] Microtubule-depolymerizing kinesin which plays a role in chromosome congression by reducing the amplitude of preanaphase oscillations and slowing poleward movement during anaphase, thus suppressing chromosome movements. May stabilize the CENPE-BUB1B complex at the kinetochores during early mitosis and maintains CENPE levels at kinetochores during chromosome congression.[1] [2] [3] [4]
Publication Abstract from PubMed
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 alpha4 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.
Insight into the molecular mechanism of the multitasking kinesin-8 motor.,Peters C, Brejc K, Belmont L, Bodey AJ, Lee Y, Yu M, Guo J, Sakowicz R, Hartman J, Moores CA EMBO J. 2010 Oct 20;29(20):3437-47. Epub 2010 Sep 3. PMID:20818331[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Mayr MI, Hummer S, Bormann J, Gruner T, Adio S, Woehlke G, Mayer TU. The human kinesin Kif18A is a motile microtubule depolymerase essential for chromosome congression. Curr Biol. 2007 Mar 20;17(6):488-98. Epub 2007 Mar 8. PMID:17346968 doi:10.1016/j.cub.2007.02.036
- ↑ Stumpff J, von Dassow G, Wagenbach M, Asbury C, Wordeman L. The kinesin-8 motor Kif18A suppresses kinetochore movements to control mitotic chromosome alignment. Dev Cell. 2008 Feb;14(2):252-62. doi: 10.1016/j.devcel.2007.11.014. PMID:18267093 doi:10.1016/j.devcel.2007.11.014
- ↑ Gardner MK, Odde DJ, Bloom K. Kinesin-8 molecular motors: putting the brakes on chromosome oscillations. Trends Cell Biol. 2008 Jul;18(7):307-10. doi: 10.1016/j.tcb.2008.05.003. Epub, 2008 May 29. PMID:18513970 doi:10.1016/j.tcb.2008.05.003
- ↑ Huang Y, Yao Y, Xu HZ, Wang ZG, Lu L, Dai W. Defects in chromosome congression and mitotic progression in KIF18A-deficient cells are partly mediated through impaired functions of CENP-E. Cell Cycle. 2009 Aug 15;8(16):2643-9. Epub 2009 Aug 29. PMID:19625775
- ↑ Peters C, Brejc K, Belmont L, Bodey AJ, Lee Y, Yu M, Guo J, Sakowicz R, Hartman J, Moores CA. Insight into the molecular mechanism of the multitasking kinesin-8 motor. EMBO J. 2010 Oct 20;29(20):3437-47. Epub 2010 Sep 3. PMID:20818331 doi:10.1038/emboj.2010.220
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