7ajl
From Proteopedia
Cyrstal structure of CYRI-B/Fam49B
Structural highlights
Function[CYRIB_MOUSE] Negatively regulates RAC1 signaling and RAC1-driven cytoskeletal remodeling (PubMed:31285585). Regulates chemotaxis, cell migration and epithelial polarization by controlling the polarity, plasticity, duration and extent of protrusions. Limits Rac1 mediated activation of the Scar/WAVE complex, focuses protrusion signals and regulates pseudopod complexity by inhibiting Scar/WAVE-induced actin polymerization (By similarity). Protects against Salmonella bacterial infection. Attenuates processes such as macropinocytosis, phagocytosis and cell migration and restrict sopE-mediated bacterial entry (PubMed:31285585). Restricts also infection mediated by Mycobacterium tuberculosis and Listeria monocytogenes (PubMed:31285585). Involved in the regulation of mitochondrial dynamics and oxidative stress (PubMed:29059164).[UniProtKB:Q9NUQ9][1] [2] Publication Abstract from PubMedRac1 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-BDeltaN) and the CYRI-BDeltaN: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. Structural Basis of CYRI-B Direct Competition with Scar/WAVE Complex for Rac1.,Yelland T, Le AH, Nikolaou S, Insall R, Machesky L, Ismail S Structure. 2021 Mar 4;29(3):226-237.e4. doi: 10.1016/j.str.2020.11.003. Epub 2020, Nov 19. PMID:33217330[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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