BIROn - Birkbeck Institutional Research Online

    Structure of the dynein-2 complex and its assembly with intraflagellar transport trains

    Toropova, K. and Zalyte, R. and Mukhopadhyay, A.G. and Mladenov, M. and Carter, A.P. and Roberts, Anthony J. (2019) Structure of the dynein-2 complex and its assembly with intraflagellar transport trains. Nature Structural & Molecular Biology 26 (9), pp. 823-829. ISSN 1545-9993.

    This is the latest version of this item.

    [img] Text
    31451806 - Author's Accepted Manuscript

    Download (0B)

    Abstract

    Dynein-2 assembles with polymeric intraflagellar transport (IFT) trains to form a transport machinery crucial for cilia biogenesis and signaling. Here we recombinantly expressed the ~1.4 MDa human dynein-2 complex and solved its cryo-EM structure to near-atomic resolution. The two identical copies of the dynein-2 heavy chain are contorted into different conformations by a WDR60-WDR34 heterodimer and a block of two RB and six LC8 light chains. One heavy chain is steered into a zig-zag, which matches the periodicity of the anterograde IFT-B train. Contacts between adjacent dyneins along the train indicate a cooperative mode of assembly. Removal of the WDR60-WDR34-light chain subcomplex renders dynein-2 monomeric and relieves auto-inhibition of its motility. Our results converge on a model in which an unusual stoichiometry of non-motor subunits control dynein-2 assembly, asymmetry, and activity, giving mechanistic insight into dynein-2’s interaction with IFT trains and the origin of diverse functions in the dynein family.

    Metadata

    Item Type: Article
    Keyword(s) / Subject(s): Cryo-EM, dynein, cilia, intraflagellar transport, motor protein
    School: School of Science > Biological Sciences
    Research Centres and Institutes: Structural Molecular Biology, Institute of (ISMB)
    Depositing User: Anthony Roberts
    Date Deposited: 03 Mar 2020 12:32
    Last Modified: 03 Mar 2020 12:32
    URI: https://eprints.bbk.ac.uk/id/eprint/29776

    Available Versions of this Item

    • Structure of the dynein-2 complex and its assembly with intraflagellar transport trains. (deposited 03 Mar 2020 12:32) [Currently Displayed]

    Statistics

    Downloads
    Activity Overview
    0Downloads
    62Hits

    Additional statistics are available via IRStats2.

    Archive Staff Only (login required)

    Edit/View Item Edit/View Item