BIROn - Birkbeck Institutional Research Online

    Cryo-EM structure of the Ustilago maydis kinesin-5 motor domain bound to microtubules

    von Loeffelholz, O. and Moores, Carolyn A. (2019) Cryo-EM structure of the Ustilago maydis kinesin-5 motor domain bound to microtubules. Journal of Structural Biology , ISSN 1047-8477. (In Press)

    [img] Text
    28033.pdf - Author's Accepted Manuscript
    Restricted to Repository staff only
    Available under License Creative Commons Attribution Non-commercial No Derivatives.

    Download (1MB) | Request a copy
    [img]
    Preview
    Text
    28033a.pdf - Published Version of Record
    Available under License Creative Commons Attribution.

    Download (1MB) | Preview

    Abstract

    In many eukaryotes, kinesin-5 motors are essential for mitosis, and small molecules that inhibit human kinesin-5 disrupt cell division. To investigate whether fungal kinesin-5s could be targets for novel fungicides, we studied kinesin-5 from the pathogenic fungus Ustilago maydis. We used cryo-electron microscopy to determine the microtubule-bound structure of its motor domain with and without the N-terminal extension. The ATP-like conformations of the motor in the presence or absence of this N-terminus are very similar, suggesting this region is structurally disordered and does not directly influence the motor ATPase. The Ustilago maydis kinesin-5 motor domain adopts a canonical ATP-like conformation, thereby allowing the neck linker to bind along the motor domain towards the microtubule plus end. However, several insertions within this motor domain are structurally distinct. Loop2 forms a non-canonical interaction with α-tubulin, while loop8 may bridge between two adjacent protofilaments. Furthermore, loop5 - which in human kinesin-5 is involved in binding allosteric inhibitors - protrudes above the nucleotide binding site, revealing a distinct binding pocket for potential inhibitors. This work highlights fungal-specific elaborations of the kinesin-5 motor domain and provides the structural basis for future investigations of kinesins as targets for novel fungicides.

    Metadata

    Item Type: Article
    School: Birkbeck Schools and Departments > School of Science > Biological Sciences
    Depositing User: Administrator
    Date Deposited: 08 Jul 2019 07:17
    Last Modified: 14 Feb 2020 21:35
    URI: http://eprints.bbk.ac.uk/id/eprint/28033

    Statistics

    Downloads
    Activity Overview
    78Downloads
    48Hits

    Additional statistics are available via IRStats2.

    Archive Staff Only (login required)

    Edit/View Item Edit/View Item