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    The divergent mitotic kinesin MKLP2 exhibits atypical structure and mechanochemistry

    Atherton, Joseph and Yu, I-M. and Cook, Alexander and Muretta, J. and Joseph, Agnel Praveen and Major, J. and Sourigues, Y. and Clause, J. and Topf, Maya and Rosenfeld, S. and Houdusse, A. and Moores, Carolyn A. (2017) The divergent mitotic kinesin MKLP2 exhibits atypical structure and mechanochemistry. eLife , ISSN 2050-084X.

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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.

    Metadata

    Item Type: Article
    Keyword(s) / Subject(s): cryo-EM, microtubules, kinesin, structural biology, mitosis
    School: Birkbeck Schools and Departments > School of Science > Biological Sciences
    Depositing User: Carolyn Moores
    Date Deposited: 15 Aug 2017 07:40
    Last Modified: 30 Jul 2019 14:00
    URI: http://eprints.bbk.ac.uk/id/eprint/19333

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