BIROn - Birkbeck Institutional Research Online

    Mapping the processivity determinants of the kinesin-3 motor domain

    Scarabelli, G. and Soppina, V. and Yao, X. and Atherton, J. and Moores, Carolyn A. and Verhey, K.J. and Grant, B.J. (2015) Mapping the processivity determinants of the kinesin-3 motor domain. Biophysical Journal 109 (8), pp. 1537-1540. ISSN 0006-3495.

    [img] Text
    12887a.pdf - Supplemental Material
    Restricted to Repository staff only

    Download (3MB)
    [img] Text
    12887.pdf - Author's Accepted Manuscript
    Restricted to Repository staff only

    Download (570kB)
    [img]
    Preview
    Text
    12887b.pdf - Published Version of Record
    Available under License Creative Commons Attribution.

    Download (577kB) | Preview

    Abstract

    Kinesin superfamily members play important roles in many diverse cellular processes, including cell motility, cell division, intracellular transport, and regulation of the microtubule cytoskeleton. How the properties of the family-defining motor domain of distinct kinesins are tailored to their different cellular roles remains largely unknown. Here, we employed molecular-dynamics simulations coupled with energetic calculations to infer the family-specific interactions of kinesin-1 and kinesin-3 motor domains with microtubules in different nucleotide states. We then used experimental mutagenesis and single-molecule motility assays to further assess the predicted residue-wise determinants of distinct kinesin-microtubule binding properties. Collectively, our results identify residues in the L8, L11, and α6 regions that contribute to family-specific microtubule interactions and whose mutation affects motor-microtubule complex stability and processive motility (the ability of an individual motor to take multiple steps along its microtubule filament). In particular, substitutions of prominent kinesin-3 residues with those found in kinesin-1, namely, R167S/H171D, K266D, and R346M, were found to decrease kinesin-3 processivity 10-fold and thus approach kinesin-1 levels.

    Metadata

    Item Type: Article
    School: Birkbeck Faculties and Schools > Faculty of Science > School of Natural Sciences
    Research Centres and Institutes: Structural Molecular Biology, Institute of (ISMB)
    Depositing User: Administrator
    Date Deposited: 22 Oct 2015 13:08
    Last Modified: 02 Aug 2023 17:18
    URI: https://eprints.bbk.ac.uk/id/eprint/12887

    Statistics

    Activity Overview
    6 month trend
    408Downloads
    6 month trend
    247Hits

    Additional statistics are available via IRStats2.

    Archive Staff Only (login required)

    Edit/View Item Edit/View Item