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Mechanism of dynein-2 in intraflagellar transport - 8 March 2022

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Speaker Dr Katerina Toropova, Postdoctoral Research Fellow, Birkbeck, University of London

Title Mechanism of dynein-2 in intraflagellar transport

Host Joe Atherton

Abstract Cilia/flagella are present on virtually all eukaryotic cells and have essential roles in signalling, sensing and cellular propulsion. The motor protein complex dynein-2 works with polymeric intraflagellar transport (IFT) trains to form a transport machinery crucial for cilia biogenesis and function. We have used cryo-electron microscopy (cryo-EM) and machine learning methods to visualise dynein-2 motor domains undergoing ATP-driven conformational changes used to power retrograde IFT, and investigated the structural adaptations of this activity in the retina. We have also recombinantly expressed and purified the full human dynein-2 complex and investigated its structure using cryo-EM revealing a 1.4 MDa assembly. The structure along with in vitro motility assays and live cell imaging, provide insights into how dynein-2’s motor activity is regulated, and how the complex recognizes the IFT train. These data give mechanistic insight into intraflagellar transport and the origin of diverse functions in the dynein family.

Image credit: Anthony Roberts and Bara Krautz

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