Campus Units

Biochemistry, Biophysics and Molecular Biology, Roy J. Carver Department of

Document Type

Article

Publication Version

Published Version

Publication Date

2017

Journal or Book Title

eLife

Volume

6

First Page

e29795

DOI

10.7554/eLife.29795

Abstract

The Rho GTPase Rac1 activates the WAVE regulatory complex (WRC) to drive Arp2/3 complex-mediated actin polymerization, which underpins diverse cellular processes. Here we report the structure of a WRC-Rac1 complex determined by cryo-electron microscopy. Surprisingly, Rac1 is not located at the binding site on the Sra1 subunit of the WRC previously identified by mutagenesis and biochemical data. Rather, it binds to a distinct, conserved site on the opposite end of Sra1. Biophysical and biochemical data on WRC mutants confirm that Rac1 binds to both sites, with the newly identified site having higher affinity and both sites required for WRC activation. Our data reveal that the WRC is activated by simultaneous engagement of two Rac1 molecules, suggesting a mechanism by which cells may sense the density of active Rac1 at membranes to precisely control actin assembly.

Comments

This article is published as Chen, Baoyu, Hui-Ting Chou, Chad A. Brautigam, Wenmin Xing, Sheng Yang, Lisa Henry, Lynda K. Doolittle, Thomas Walz, and Michael K. Rosen. "Rac1 GTPase activates the WAVE regulatory complex through two distinct binding sites." Elife 6 (2017): e29795. doi: 10.7554/eLife.29795.

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

Copyright Owner

Chen et al.

Language

en

File Format

application/pdf

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