Yelland, Tamas;
Le, Anh Hoang;
Nikolaou, Savvas;
Insall, Robert;
Machesky, Laura;
Ismail, Shehab;
(2021)
Structural Basis of CYRI-B Direct Competition with Scar/WAVE Complex for Rac1.
Structure
, 29
(3)
226-237.e4.
10.1016/j.str.2020.11.003.
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Structural Basis of CYRI-B Direct Competition with Scar:WAVE Complex for Rac1.pdf - Published Version Download (7MB) | Preview |
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.
| Type: | Article |
|---|---|
| Title: | Structural Basis of CYRI-B Direct Competition with Scar/WAVE Complex for Rac1 |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.str.2020.11.003 |
| Publisher version: | https://doi.org/10.1016/j.str.2020.11.003 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third-party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | CYRIB, SCAR/WAVE, actin, cytoskeleton, invasion, rho, Adaptor Proteins, Signal Transducing, Animals, Binding Sites, COS Cells, Chlorocebus aethiops, Conserved Sequence, Humans, Intracellular Signaling Peptides and Proteins, Mice, Mitochondrial Proteins, Molecular Docking Simulation, Protein Binding, rac1 GTP-Binding Protein |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10176007 |
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