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The divergent mitotic kinesin MKLP2 exhibits atypical structure and mechanochemistry

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. Green open access

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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 > Provost and Vice Provost Offices
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: http://discovery.ucl.ac.uk/id/eprint/10073444
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