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