Atherton, J;
Yu, I-M;
Cook, A;
Muretta, JM;
Joseph, A;
Major, J;
Sourigues, Y;
... Moores, CA; + view all
(2017)
The divergent mitotic kinesin MKLP2 exhibits atypical structure and mechanochemistry.
eLIFE
, 6
, Article e27793. 10.7554/eLife.27793.
Preview |
Text
elife-27793-v3.pdf - Published Version Download (8MB) | Preview |
Abstract
MKLP2, a kinesin-6, has critical roles during the metaphase-anaphase transition and cytokinesis. Its motor domain contains conserved nucleotide binding motifs, but is divergent in sequence (~35% identity) and size (~40% larger) compared to other kinesins. Using cryo-electron microscopy and biophysical assays, we have undertaken a mechanochemical dissection of the microtubule-bound MKLP2 motor domain during its ATPase cycle, and show that many facets of its mechanism are distinct from other kinesins. While the MKLP2 neck-linker is directed towards the microtubule plus-end in an ATP-like state, it does not fully dock along the motor domain. Furthermore, the footprint of the MKLP2 motor domain on the MT surface is altered compared to motile kinesins, and enhanced by kinesin-6-specific sequences. The conformation of the highly extended loop6 insertion characteristic of kinesin-6s is nucleotide-independent and does not contact the MT surface. Our results emphasize the role of family-specific insertions in modulating kinesin motor function.
Type: | Article |
---|---|
Title: | The divergent mitotic kinesin MKLP2 exhibits atypical structure and mechanochemistry |
Open access status: | An open access version is available from UCL Discovery |
DOI: | 10.7554/eLife.27793 |
Publisher version: | https://doi.org/10.7554/eLife.27793.001 |
Language: | English |
Additional information: | © 2019 eLife Sciences Publications Ltd. Subject to a Creative Commons Attribution license, except where otherwise noted. ISSN: 2050-084X |
UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology |
URI: | https://discovery.ucl.ac.uk/id/eprint/10073444 |
Archive Staff Only
![]() |
View Item |