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Structure of CYRI-B (FAM49B), a key regulator of cellular actin assembly

DOI: 10.1107/S2059798320010906 DOI Help

Authors: Elise Kaplan (University of Cambridge) , Rachael Stone (University of Cambridge) , Peter J. Hume (University of Cambridge) , Nicholas Greene (University of Cambridge) , Vassilis Koronakis (University of Cambridge)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Acta Crystallographica Section D Structural Biology , VOL 76 , PAGES 1015 - 1024

State: Published (Approved)
Published: October 2020

Open Access Open Access

Abstract: 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.

Journal Keywords: CYRI-B; FAM49B; actin assembly; cell-motility regulator; SAD; crystal structure

Subject Areas: Biology and Bio-materials

Instruments: I03-Macromolecular Crystallography

Added On: 30/09/2020 13:23


Discipline Tags:

Structural biology Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)