Structures reveal a key mechanism of WAVE regulatory complex activation by Rac1 GTPase

Bojian Ding, Sheng Yang, Matthias Schaks, Yijun Liu, Abbigale J. Brown, Klemens Rottner, Saikat Chowdhury () and Baoyu Chen ()
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Bojian Ding: Stony Brook University
Sheng Yang: Iowa State University
Matthias Schaks: Technische Universität Braunschweig
Yijun Liu: Iowa State University
Abbigale J. Brown: Iowa State University
Klemens Rottner: Technische Universität Braunschweig
Saikat Chowdhury: Stony Brook University
Baoyu Chen: Iowa State University

Nature Communications, 2022, vol. 13, issue 1, 1-13

Abstract: Abstract The Rho-family GTPase Rac1 activates the WAVE regulatory complex (WRC) to drive Arp2/3 complex-mediated actin polymerization in many essential processes. Rac1 binds to WRC at two distinct sites—the A and D sites. Precisely how Rac1 binds and how the binding triggers WRC activation remain unknown. Here we report WRC structures by itself, and when bound to single or double Rac1 molecules, at ~3 Å resolutions by cryogenic-electron microscopy. The structures reveal that Rac1 binds to the two sites by distinct mechanisms, and binding to the A site, but not the D site, drives WRC activation. Activation involves a series of unique conformational changes leading to the release of sequestered WCA (WH2-central-acidic) polypeptide, which stimulates the Arp2/3 complex to polymerize actin. Together with biochemical and cellular analyses, the structures provide a novel mechanistic understanding of how the Rac1-WRC-Arp2/3-actin signaling axis is regulated in diverse biological processes and diseases.

Date: 2022
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33174-3

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DOI: 10.1038/s41467-022-33174-3

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