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.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Copyright Owner
Chen et al.
Copyright Date
2017
Language
en
File Format
application/pdf
Recommended Citation
Chen, Baoyu; Chou, Hui-Ting; Brautigam, Chad A.; Xing, Wenmin; Yang, Sheng; Henry, Lisa; Doolittle, Lynda K.; Walz, Thomas; and Rosen, Michael K., "Rac1 GTPase activates the WAVE regulatory complex through two distinct binding sites" (2017). Biochemistry, Biophysics and Molecular Biology Publications. 222.
https://lib.dr.iastate.edu/bbmb_ag_pubs/222
Included in
Biochemistry Commons, Biophysics Commons, Molecular Biology Commons, Structural Biology Commons
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.