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Significance Actin filament nucleation by Arp2/3 complex must be triggered by activators like WASP family proteins. Understanding how WASP proteins activate Arp2/3 complex has been a major challenge due to… Click to show full abstract
Significance Actin filament nucleation by Arp2/3 complex must be triggered by activators like WASP family proteins. Understanding how WASP proteins activate Arp2/3 complex has been a major challenge due to a lack of high-resolution structures of the complex in an activated state. We determined a high-resolution (∼3.9 Å) structure of the WASP-activated Arp2/3 complex at a branch junction and used biochemical, cell biological, and molecular dynamic simulations to understand the mechanism of WASP-mediated activation. This work shows in detail the contacts between the fully activated Arp2/3 complex, the nucleated daughter actin filament, and the mother actin filament and provides important insights into how conformational rearrangements in the Arp2/3 complex are stimulated during activation.
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Year Published: 2022
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