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

Acta Crystallogr D Struct Biol. 2020 Oct 1;76(Pt 10):1015-1024. doi: 10.1107/S2059798320010906. Epub 2020 Sep 23.

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.

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

MeSH terms

  • Animals
  • Crystallography, X-Ray
  • Intracellular Signaling Peptides and Proteins / chemistry*
  • Mitochondrial Proteins / chemistry*
  • Protein Conformation, alpha-Helical
  • Protein Domains
  • Sharks

Substances

  • Intracellular Signaling Peptides and Proteins
  • Mitochondrial Proteins