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

Structure
Tamas YellandShehab Ismail

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.

References

Nov 25, 2000·Molecular Cell·K LapougeK Rittinger
May 1, 1997·Acta Crystallographica. Section D, Biological Crystallography·G N MurshudovE J Dodson
Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·Paul Emsley, Kevin Cowtan
Aug 8, 2007·Journal of Molecular Biology·Evgeny Krissinel, Kim Henrick
Nov 17, 2007·The Journal of Biological Chemistry·Rakhee ModhaHelen R Mott
Jul 5, 2008·Nature Protocols·Gerrit LangerAnastassis Perrakis
Apr 13, 2010·Acta Crystallographica. Section D, Biological Crystallography·P EmsleyK Cowtan
Nov 26, 2010·Nature·Zhucheng ChenMichael K Rosen
Jan 25, 2011·Current Biology : CB·Andrew J Davidson, Robert H Insall
Apr 5, 2011·Acta Crystallographica. Section D, Biological Crystallography·Martyn D WinnKeith S Wilson
Jul 24, 2012·Cell·Eran HodisLynda Chin
Jul 31, 2012·Nature Genetics·Michael KrauthammerRuth Halaban
Aug 15, 2012·The Journal of Cell Biology·Douwe M VeltmanRobert H Insall
Jan 4, 2013·Proceedings of the National Academy of Sciences of the United States of America·Matthew J DavisTitus J Boggon
Mar 4, 2014·Nature Structural & Molecular Biology·David J KastRoberto Dominguez
Aug 26, 2014·Nature Reviews. Molecular Cell Biology·Matthias Krause, Alexis Gautreau
Apr 11, 2018·Proceedings of the National Academy of Sciences of the United States of America·Wanjing ShangHaopeng Wang
Sep 27, 2018·Nature Cell Biology·Loic FortLaura M Machesky
Aug 16, 2019·Communicative & Integrative Biology·Jamie A WhitelawLaura M Machesky
Oct 14, 2019·Protein Science : a Publication of the Protein Society·Liisa Holm

❮ Previous
Next ❯

Citations

Jun 25, 2021·The Journal of Cell Biology·Anh Hoang LeLaura M Machesky

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.