Structural Basis of CYRI-B Direct Competition with Scar/WAVE Complex for Rac1

Overview

Journal Structure

Publisher Cell Press

Specialties Biochemistry
Biotechnology
Cell Biology
Molecular Biology

Date 2020 Nov 20

PMID 33217330

Citations 8

Authors

Tamas Yelland

Anh Hoang Le

Savvas Nikolaou

Robert Insall

Laura Machesky

Shehab Ismail

Affiliations

Soon will be listed here.

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.

Citing Articles

CYRI controls epidermal wound closure and cohesion of invasive border cell cluster in Drosophila.

Rotte M, Hohne M, Klug D, Ramlow K, Zedler C, Lehne F J Cell Biol. 2024; 223(12).

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CYRI-B-mediated macropinocytosis drives metastasis via lysophosphatidic acid receptor uptake.

Nikolaou S, Juin A, Whitelaw J, Paul N, Fort L, Nixon C Elife. 2024; 13.

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PPP2R1A regulates migration persistence through the NHSL1-containing WAVE Shell Complex.

Wang Y, Chiappetta G, Guerois R, Liu Y, Romero S, Boesch D Nat Commun. 2023; 14(1):3541.

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Rac1: A Regulator of Cell Migration and a Potential Target for Cancer Therapy.

Ma N, Xu E, Luo Q, Song G Molecules. 2023; 28(7).

PMID: 37049739 PMC: 10096471. DOI: 10.3390/molecules28072976.

CYRI proteins: controllers of actin dynamics in the cellular 'eat vs walk' decision.

Machesky L Biochem Soc Trans. 2023; 51(2):579-585.

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