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

DOI: 10.1038/s41594-019-0286-y

Authors: Katerina Toropova (Birkbeck, University of London) , Ruta Zalyte (Medical Research Council Laboratory of Molecular Biology) , Aakash G. Mukhopadhyay (Birkbeck, University of London) , Miroslav Mladenov (Birkbeck, University of London) , Andrew Carter (Medical Research Council Laboratory of Molecular Biology) , Anthony J. Roberts (Birkbeck, University of London)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Structural & Molecular Biology , VOL 26 , PAGES 823 - 829

State: Published (Approved)
Published: August 2019
Diamond Proposal Number(s): 14704

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.

Journal Keywords: Cilia; Cryoelectron microscopy; Dynein; Motor protein structure

Subject Areas: Biology and Bio-materials

Diamond Offline Facilities: Electron Bio-Imaging Centre (eBIC)
Instruments: Krios I-Titan Krios I at Diamond , Krios II-Titan Krios II at Diamond , Krios III-Titan Krios III at Diamond , Krios IV-Titan Krios IV at Diamond , Krios V-Titan Krios V at Diamond

Added On: 12/09/2019 14:07

Discipline Tags:

Structural biology Life Sciences & Biotech

Technical Tags:

Microscopy Electron Microscopy (EM) Cryo Electron Microscopy (Cryo EM)