4RM9

Crystal structure of human ezrin in space group C2221

Summary for 4RM9

• Entry DOI: 10.2210/pdb4rm9/pdb
• Related: 4RM8 4RMA
• Descriptor: Ezrin (2 entities in total)
• Functional Keywords: ferm domain, c-ermad domain, membrane cytoskeleton linkers, actin binding, peptide binding protein
• Biological source: Homo sapiens (human)
• Cellular location: Apical cell membrane ; Peripheral membrane protein ; Cytoplasmic side : P15311
• Total number of polymer chains: 1
• Total formula weight: 69583.97

Authors

Phang, J.M.,Harrop, S.J.,Davies, R.,Duff, A.P.,Wilk, K.E.,Curmi, P.M.G. (deposition date: 2014-10-21, release date: 2015-12-09, Last modification date: 2023-09-20)

Primary citation

Phang, J.M.,Harrop, S.J.,Duff, A.P.,Sokolova, A.V.,Crossett, B.,Walsh, J.C.,Beckham, S.A.,Nguyen, C.D.,Davies, R.B.,Glockner, C.,Bromley, E.H.,Wilk, K.E.,Curmi, P.M.
Structural characterization suggests models for monomeric and dimeric forms of full-length ezrin.
Biochem. J., 473:2763-2782, 2016

PubMed Abstract: Ezrin is a member of the ERM (ezrin-radixin-moesin) family of proteins that have been conserved through metazoan evolution. These proteins have dormant and active forms, where the latter links the actin cytoskeleton to membranes. ERM proteins have three domains: an N-terminal FERM [band Four-point-one (4.1) ERM] domain comprising three subdomains (F1, F2, and F3); a helical domain; and a C-terminal actin-binding domain. In the dormant form, FERM and C-terminal domains form a stable complex. We have determined crystal structures of the active FERM domain and the dormant FERM:C-terminal domain complex of human ezrin. We observe a bistable array of phenylalanine residues in the core of subdomain F3 that is mobile in the active form and locked in the dormant form. As subdomain F3 is pivotal in binding membrane proteins and phospholipids, these transitions may facilitate activation and signaling. Full-length ezrin forms stable monomers and dimers. We used small-angle X-ray scattering to determine the solution structures of these species. As expected, the monomer shows a globular domain with a protruding helical coiled coil. The dimer shows an elongated dumbbell structure that is twice as long as the monomer. By aligning ERM sequences spanning metazoan evolution, we show that the central helical region is conserved, preserving the heptad repeat. Using this, we have built a dimer model where each monomer forms half of an elongated antiparallel coiled coil with domain-swapped FERM:C-terminal domain complexes at each end. The model suggests that ERM dimers may bind to actin in a parallel fashion.

PubMed: 27364155
DOI: 10.1042/BCJ20160541

Experimental method

X-RAY DIFFRACTION (2 Å)