| 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 PubMed
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-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
- ↑ Chattaragada MS, Riganti C, Sassoe M, Principe M, Santamorena MM, Roux C, Curcio C, Evangelista A, Allavena P, Salvia R, Rusev B, Scarpa A, Cappello P, Novelli F. FAM49B, a novel regulator of mitochondrial function and integrity that suppresses tumor metastasis. Oncogene. 2018 Feb 8;37(6):697-709. doi: 10.1038/onc.2017.358. Epub 2017 Oct 23. PMID:29059164 doi:http://dx.doi.org/10.1038/onc.2017.358
- ↑ Yuki KE, Marei H, Fiskin E, Eva MM, Gopal AA, Schwartzentruber JA, Majewski J, Cellier M, Mandl JN, Vidal SM, Malo D, Dikic I. CYRI/FAM49B negatively regulates RAC1-driven cytoskeletal remodelling and protects against bacterial infection. Nat Microbiol. 2019 Sep;4(9):1516-1531. doi: 10.1038/s41564-019-0484-8. Epub 2019, Jul 8. PMID:31285585 doi:http://dx.doi.org/10.1038/s41564-019-0484-8
- ↑ Yelland T, Le AH, Nikolaou S, Insall R, Machesky L, Ismail S. Structural Basis of CYRI-B Direct Competition with Scar/WAVE Complex for Rac1. Structure. 2021 Mar 4;29(3):226-237.e4. doi: 10.1016/j.str.2020.11.003. Epub 2020, Nov 19. PMID:33217330 doi:http://dx.doi.org/10.1016/j.str.2020.11.003
|
