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.
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A merged immunofluorescence microscope image of meiotic chromosome spread from testes excised from wild-type male mice, stained with antibodies against phospho-gamma-H2AX (green) to detect DNA damage and Sycp3 (red) to determine the stage of progression of cells during synapsis. Cells were counter-stained with DAPI (blue). Images were visualized and taken using Zeiss AxioImager Z1 epifluorescence microscope with Zeiss AxioCam MRc5 at 63X objective (Zeiss Plan-APOCHROMAT, 63x/1.4 Oil DIC, ∞/0.17). Photo was taken by Joanna H.S. Lee and Philipp Kaldis, Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Singapore. Image kindly supplied by Philipp Kaldis. For further details see pages 2783–2798
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Structural characterization suggests models for monomeric and dimeric forms of full-length ezrin
Juanita M. Phang, Stephen J. Harrop, Anthony P. Duff, Anna V. Sokolova, Ben Crossett, James C. Walsh, Simone A. Beckham, Cuong D. Nguyen, Roberta B. Davies, Carina Glöckner, Elizabeth H.C. Bromley, Krystyna E. Wilk, Paul M.G. Curmi; Structural characterization suggests models for monomeric and dimeric forms of full-length ezrin. Biochem J 15 September 2016; 473 (18): 2763–2782. doi: https://doi.org/10.1042/BCJ20160541
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