Structure of CYRI-B (FAM49B), a key regulator of cellular actin assembly.
In eukaryotes, numerous fundamental processes are controlled by the WAVE regulatory complex (WRC) that regulates cellular actin polymerization, crucial for cell motility, cell-cell adhesion and epithelial differentiation. Actin assembly is triggered by interaction of the small GTPase Rac1 with CYFIP1, a key component of the WRC. Previously known as FAM49B, CYRI-B is a protein that is highly conserved across the Eukaryota and has recently been revealed to be a key regulator of Rac1 activity. Mutation of CYRI-B or alteration of its expression therefore leads to altered actin nucleation dynamics, with impacts on lamellipodia formation, cell migration and infection by intracellular pathogens. In addition, knockdown of CYRI-B expression in cancer cell lines results in accelerated cell proliferation and invasiveness. Here, the structure of Rhincodon typus (whale shark) CYRI-B is presented, which is the first to be reported of any CYRI family member. Solved by X-ray crystallography, the structure reveals that CYRI-B comprises three distinct α-helical subdomains and is highly structurally related to a conserved domain present in CYFIP proteins. The work presented here establishes a template towards a better understanding of CYRI-B biological function.
['Kaplan|Elise|E|0000-0003-4985-1482', 'Stone|Rachael|R|0000-0002-3320-8073', 'Hume|Peter J|PJ|0000-0002-4064-4519', 'Greene|Nicholas P|NP|0000-0002-3631-0380', 'Koronakis|Vassilis|V|0000-0002-1353-1092']
D000818:Animals D018360:Crystallography, X-Ray D047908:Intracellular Signaling Peptides and Proteins D024101:Mitochondrial Proteins D000072756:Protein Conformation, alpha-Helical D000072417:Protein Domains D012754:Sharks
CYRI-B FAM49B actin assembly SAD cell-motility regulator crystal structure