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    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.

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    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: Birkbeck Faculties and Schools > Faculty of Science > School of Natural Sciences
    Research Centres and Institutes: Structural Molecular Biology, Institute of (ISMB)
    Depositing User: Anthony Roberts
    Date Deposited: 03 Mar 2020 12:32
    Last Modified: 02 Aug 2023 17:55
    URI: https://eprints.bbk.ac.uk/id/eprint/29776

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