Structural basis of adhesion-molecule recognition by ERM proteins revealed by the crystal structure of the radixin-ICAM-2 complex

EMBO J. 2003 Feb 3;22(3):502-14. doi: 10.1093/emboj/cdg039.

Abstract

ERM (ezrin/radixin/moesin) proteins recognize the cytoplasmic domains of adhesion molecules in the formation of the membrane-associated cytoskeleton. Here we report the crystal structure of the radixin FERM (4.1 and ERM) domain complexed with the ICAM-2 cytoplasmic peptide. The non-polar region of the ICAM-2 peptide contains the RxxTYxVxxA sequence motif to form a beta-strand followed by a short 3(10)-helix. It binds the groove of the phosphotyrosine-binding (PTB)-like subdomain C mediated by a beta-beta association and several side-chain interactions. The binding mode of the ICAM-2 peptide to the FERM domain is distinct from that of the NPxY motif-containing peptide binding to the canonical PTB domain. Mutation analyses based on the crystal structure reveal the determinant elements of recognition and provide the first insights into the physical link between adhesion molecules and ERM proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, CD / chemistry*
  • Antigens, CD / genetics
  • Antigens, CD / metabolism
  • Blood Proteins / chemistry*
  • Blood Proteins / genetics
  • Blood Proteins / metabolism
  • Cell Adhesion Molecules / chemistry*
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism
  • Cell Membrane / metabolism
  • Crystallography, X-Ray
  • Cytoskeletal Proteins / chemistry*
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism
  • Cytoskeleton / metabolism
  • Humans
  • Macromolecular Substances
  • Membrane Proteins / chemistry*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • Molecular Structure
  • Mutation
  • Peptides / chemistry
  • Peptides / genetics
  • Peptides / metabolism
  • Protein Binding
  • Protein Structure, Secondary*
  • Protein Structure, Tertiary*
  • Sequence Alignment
  • Trans-Activators / chemistry
  • Trans-Activators / metabolism
  • beta Catenin

Substances

  • Antigens, CD
  • Blood Proteins
  • CTNNB1 protein, human
  • CTNNB1 protein, mouse
  • Cell Adhesion Molecules
  • Cytoskeletal Proteins
  • ICAM2 protein, human
  • Macromolecular Substances
  • Membrane Proteins
  • Peptides
  • Trans-Activators
  • beta Catenin
  • radixin

Associated data

  • PDB/1J19