2. Academic Validation
  3. Structure of the dynein-2 complex and its assembly with intraflagellar transport trains

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

  • Nat Struct Mol Biol. 2019 Sep;26(9):823-829. doi: 10.1038/s41594-019-0286-y.
Katerina Toropova 1,  Ruta Zalyte 2,  Aakash G Mukhopadhyay 1,  Miroslav Mladenov 1,  Andrew P Carter 2,  Anthony J Roberts 3
Affiliations

Affiliations

  • 1 Institute of Structural and Molecular Biology, Birkbeck, University of London, London, UK.
  • 2 Medical Research Council Laboratory of Molecular Biology, Division of Structural Studies, Cambridge, UK.
  • 3 Institute of Structural and Molecular Biology, Birkbeck, University of London, London, UK. [email protected].
PMID: 31451806 DOI: 10.1038/s41594-019-0286-y
Abstract

Dynein-2 assembles with polymeric intraflagellar transport (IFT) trains to form a transport machinery that is 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 conformation, 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 autoinhibition of its motility. Our results converge on a model in which an unusual stoichiometry of non-motor subunits controls dynein-2 assembly, asymmetry, and activity, giving mechanistic insight into the interaction of dynein-2 with IFT trains and the origin of diverse functions in the dynein family.

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