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Structural basis of CYRI-B direct competition with Scar/WAVE complex for Rac1

DOI: 10.1016/j.str.2020.11.003 DOI Help

Authors: Tamas Yelland (CRUK- Beatson Institute) , Anh Hoang Le (CRUK- Beatson Institute) , Savvas Nikolaou (CRUK- Beatson Institute) , Robert Insall (CRUK- Beatson Institute; University of Glasgow) , Laura Machesky (CRUK- Beatson Institute; University of Glasgow) , Shehab Ismail (CRUK - Beatson Institute; University of Glasgow; KU Leuven)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Structure

State: Published (Approved)
Published: November 2020

Open Access Open Access

Abstract: Rac1 is a major regulator of actin dynamics, with GTP-bound Rac1 promoting actin assembly via the Scar/WAVE complex. CYRI competes with Scar/WAVE for interaction with Rac1 in a feedback loop regulating actin dynamics. Here, we reveal the nature of the CYRI-Rac1 interaction, through crystal structures of CYRI-B lacking the N-terminal helix (CYRI-BΔN) and the CYRI-BΔN:Rac1Q61L complex, providing the molecular basis for CYRI-B regulation of the Scar/WAVE complex. We reveal CYRI-B as having two subdomains - an N-terminal Rac1 binding subdomain with a unique Rac1-effector interface and a C-terminal Ratchet subdomain that undergoes conformational changes induced by Rac1 binding. Finally, we show that the CYRI protein family, CYRI-A and CYRI-B can produce an autoinhibited hetero- or homodimers, adding an additional layer of regulation to Rac1 signaling.

Journal Keywords: rho; actin; CYRIB; SCAR/WAVE; cytoskeleton; invasion

Subject Areas: Biology and Bio-materials


Instruments: I03-Macromolecular Crystallography , I04-Macromolecular Crystallography

Documents:
1-s2.0-S0969212620304159-main.pdf