The divergent mitotic kinesin MKLP2 exhibits atypical structure and mechanochemistry
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.
Data availability
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14-protofilament microtubule-bound mammalian MKLP2 motor domain with ADPPublicly available at Protein Data Bank in Europe (accession no: EMD-3620).
Article and author information
Author details
Funding
Medical Research Council (MR/J000973/1)
- Carolyn A Moores
Medical Research Council (MR/J003867/1)
- Alexander Cook
Medical Research Council (MR/M019292/1)
- Maya Topf
American Heart Association (SDG20480032)
- Joseph M Muretta
National Institute of General Medical Sciences (GM102875 NS073610)
- Steven S Rosenfeld
Centre National de la Recherche Scientifique
- Anne Houdusse
Agence Nationale de la Recherche
- Anne Houdusse
Ligue Contre le Cancer
- Anne Houdusse
European Commission (Marie Curie Fellowship)
- I-Mei Yu
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Edward H Egelman, University of Virginia, United States
Version history
- Received: April 15, 2017
- Accepted: August 7, 2017
- Accepted Manuscript published: August 11, 2017 (version 1)
- Version of Record published: September 18, 2017 (version 2)
- Version of Record updated: March 12, 2019 (version 3)
Copyright
© 2017, Atherton et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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