Structure of the ERM Protein Moesin Reveals the FERM Domain Fold Masked by an Extended Actin Binding Tail Domain

• Published in: Cell Vol. 101; no. 3; pp. 259 - 270
• Main Authors: Pearson, Matthew A., Reczek, David, Bretscher, Anthony, Karplus, P.Andrew
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 28-04-2000
• Subjects: Actins - metabolism; Amino Acid Sequence; Binding Sites; Crystallography, X-Ray; Cytoskeletal Proteins; ERM protein; Humans; Membrane Proteins - chemistry; merlin protein; Microfilament Proteins - chemistry; Microfilament Proteins - genetics; Microfilament Proteins - metabolism; Models, Molecular; moesin; Molecular Sequence Data; Neurofibromin 2; Neuropeptides; Protein Folding; Protein Structure, Tertiary; Recombinant Fusion Proteins - chemistry; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - metabolism
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/S0092-8674(00)80836-3

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.