| Structural highlights
Function
[EZRI_HUMAN] Probably involved in connections of major cytoskeletal structures to the plasma membrane. In epithelial cells, required for the formation of microvilli and membrane ruffles on the apical pole. Along with PLEKHG6, required for normal macropinocytosis.[1] [2] [3]
Publication Abstract from PubMed
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.
Structural characterization suggests models for monomeric and dimeric forms of full-length ezrin.,Phang JM, Harrop SJ, Duff AP, Sokolova AV, Crossett B, Walsh JC, Beckham SA, Nguyen CD, Davies RB, Glockner C, Bromley EH, Wilk KE, Curmi PM Biochem J. 2016 Sep 15;473(18):2763-82. doi: 10.1042/BCJ20160541. Epub 2016 Jun, 30. PMID:27364155[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ D'Angelo R, Aresta S, Blangy A, Del Maestro L, Louvard D, Arpin M. Interaction of ezrin with the novel guanine nucleotide exchange factor PLEKHG6 promotes RhoG-dependent apical cytoskeleton rearrangements in epithelial cells. Mol Biol Cell. 2007 Dec;18(12):4780-93. Epub 2007 Sep 19. PMID:17881735 doi:http://dx.doi.org/E06-12-1144
- ↑ Wald FA, Oriolo AS, Mashukova A, Fregien NL, Langshaw AH, Salas PJ. Atypical protein kinase C (iota) activates ezrin in the apical domain of intestinal epithelial cells. J Cell Sci. 2008 Mar 1;121(Pt 5):644-54. doi: 10.1242/jcs.016246. Epub 2008 Feb, 12. PMID:18270268 doi:10.1242/jcs.016246
- ↑ Austermann J, Nazmi AR, Heil A, Fritz G, Kolinski M, Filipek S, Gerke V. Generation and characterization of a novel, permanently active S100P mutant. Biochim Biophys Acta. 2009 Jun;1793(6):1078-85. doi:, 10.1016/j.bbamcr.2008.11.012. Epub 2008 Dec 8. PMID:19111582 doi:http://dx.doi.org/10.1016/j.bbamcr.2008.11.012
- ↑ Phang JM, Harrop SJ, Duff AP, Sokolova AV, Crossett B, Walsh JC, Beckham SA, Nguyen CD, Davies RB, Glockner C, Bromley EH, Wilk KE, Curmi PM. Structural characterization suggests models for monomeric and dimeric forms of full-length ezrin. Biochem J. 2016 Sep 15;473(18):2763-82. doi: 10.1042/BCJ20160541. Epub 2016 Jun, 30. PMID:27364155 doi:http://dx.doi.org/10.1042/BCJ20160541
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