Structure of the ERM protein moesin reveals the FERM domain fold masked by an extended actin binding tail domain

Cell. 2000 Apr 28;101(3):259-70. doi: 10.1016/s0092-8674(00)80836-3.

Abstract

The ezrin-radixin-moesin (ERM) protein family link actin filaments of cell surface structures to the plasma membrane, using a C-terminal F-actin binding segment and an N-terminal FERM domain, a common membrane binding module. ERM proteins are regulated by an intramolecular association of the FERM and C-terminal tail domains that masks their binding sites. The crystal structure of a dormant moesin FERM/tail complex reveals that the FERM domain has three compact lobes including an integrated PTB/PH/ EVH1 fold, with the C-terminal segment bound as an extended peptide masking a large surface of the FERM domain. This extended binding mode suggests a novel mechanism for how different signals could produce varying levels of activation. Sequence conservation suggests a similar regulation of the tumor suppressor merlin.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Actins / metabolism*
  • Amino Acid Sequence
  • Binding Sites
  • Crystallography, X-Ray
  • Cytoskeletal Proteins*
  • Humans
  • Membrane Proteins / chemistry
  • Microfilament Proteins / chemistry*
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Neurofibromin 2
  • Neuropeptides*
  • Protein Folding*
  • Protein Structure, Tertiary
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism

Substances

  • Actins
  • Cytoskeletal Proteins
  • Membrane Proteins
  • Microfilament Proteins
  • Neurofibromin 2
  • Neuropeptides
  • Recombinant Fusion Proteins
  • erythrocyte membrane band 4.1 protein
  • erythrocyte membrane protein band 4.1-like 1
  • moesin

Associated data

  • PDB/1EF1