BIROn - Birkbeck Institutional Research Online

    Cryo-EM structure (4.5-Å) of Yeast Kinesin-5–Microtubule Complex reveals a distinct binding footprint and mechanism of drug resistance

    von Loeffelholz, O. and Peña, A. and Drummond, D.R. and Cross, R. and Moores, Carolyn A. (2019) Cryo-EM structure (4.5-Å) of Yeast Kinesin-5–Microtubule Complex reveals a distinct binding footprint and mechanism of drug resistance. Journal of Molecular Biology 431 (4), pp. 864-872. ISSN 0022-2836.

    [img] Text
    25864.pdf - Author's Accepted Manuscript
    Restricted to Repository staff only
    Available under License Creative Commons Attribution Non-commercial No Derivatives.

    Download (45MB) | Request a copy
    [img] Text
    25864a.pdf - Supplemental Material
    Restricted to Repository staff only
    Available under License Creative Commons Attribution Non-commercial No Derivatives.

    Download (3MB) | Request a copy
    [img] Text ("Article In Press" version of AAM)
    25864b.pdf - Author's Accepted Manuscript
    Restricted to Repository staff only
    Available under License Creative Commons Attribution.

    Download (2MB) | Request a copy
    [img]
    Preview
    Text
    25864c.pdf - Published Version of Record
    Available under License Creative Commons Attribution.

    Download (1MB) | Preview

    Abstract

    Kinesin-5s are microtubule-dependent motors that drive spindle pole separation during mitosis. We used cryo-electron microscopy to determine the 4.5 Å resolution structure of the motor domain of the fission yeast kinesin-5 Cut7 bound to fission yeast microtubules, and explored the topology of the motor-microtubule interface and the susceptibility of the complex to drug binding. Despite their non-canonical architecture and mechanochemistry, S. pombe microtubules were stabilized by epothilone at the taxane binding pocket. The overall Cut7 footprint on the S. pombe microtubule surface is altered compared to mammalian tubulin microtubules because of their different polymer architectures. However, the core motor-microtubule interaction is tightly conserved, reflected in similar Cut7 ATPase activities on each microtubule type. AMPPNP-bound Cut7 adopts a kinesin-conserved ATP-like conformation including cover neck bundle formation. However, the Cut7 ATPase is not blocked by a mammalian-specific kinesin-5 inhibitor, consistent with the non-conserved sequence and structure of its loop5 insertion.

    Metadata

    Item Type: Article
    Keyword(s) / Subject(s): cytoskeleton, motor, mitosis, Cut7, 3D reconstruction
    School: Birkbeck Schools and Departments > School of Science > Biological Sciences
    Depositing User: Administrator
    Date Deposited: 16 Jan 2019 12:06
    Last Modified: 16 Sep 2019 05:24
    URI: http://eprints.bbk.ac.uk/id/eprint/25864

    Statistics

    Downloads
    Activity Overview
    56Downloads
    39Hits

    Additional statistics are available via IRStats2.

    Archive Staff Only (login required)

    Edit/View Item Edit/View Item