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

Authors
  • Kaplan, Elise1
  • Stone, Rachael1
  • Hume, Peter J1
  • Greene, Nicholas P1
  • Koronakis, Vassilis1
  • 1 Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, United Kingdom. , (United Kingdom)
Type
Published Article
Journal
Acta crystallographica. Section D, Structural biology
Publication Date
Oct 01, 2020
Volume
76
Issue
Pt 10
Pages
1015–1024
Identifiers
DOI: 10.1107/S2059798320010906
PMID: 33021503
Source
Medline
Keywords
Language
English
License
Unknown

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. open access.

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