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Publication Abstract from PubMed

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 alpha-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.

Structure of CYRI-B (FAM49B), a key regulator of cellular actin assembly.,Kaplan E, Stone R, Hume PJ, Greene NP, Koronakis V Acta Crystallogr D Struct Biol. 2020 Oct 1;76(Pt 10):1015-1024. doi:, 10.1107/S2059798320010906. Epub 2020 Sep 23. PMID:33021503^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.