Structural characterization suggests models for monomeric and dimeric forms of full-length ezrin.

Autor:	Phang JM; School of Physics, The University of New South Wales, Sydney, NSW 2052, Australia., Harrop SJ; School of Physics, The University of New South Wales, Sydney, NSW 2052, Australia., Duff AP; Australian Nuclear Science and Technology Organisation, Lucas Heights, NSW 2234, Australia., Sokolova AV; Australian Nuclear Science and Technology Organisation, Lucas Heights, NSW 2234, Australia., Crossett B; Mass Spectrometry Core Facility, University of Sydney, Sydney, NSW 2006, Australia., Walsh JC; School of Physics, The University of New South Wales, Sydney, NSW 2052, Australia., Beckham SA; Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia., Nguyen CD; School of Physics, The University of New South Wales, Sydney, NSW 2052, Australia., Davies RB; School of Physics, The University of New South Wales, Sydney, NSW 2052, Australia., Glöckner C; School of Physics, The University of New South Wales, Sydney, NSW 2052, Australia., Bromley EH; Department of Physics, University of Durham, Durham, U.K., Wilk KE; School of Physics, The University of New South Wales, Sydney, NSW 2052, Australia., Curmi PM; School of Physics, The University of New South Wales, Sydney, NSW 2052, Australia Centre for Applied Medical Research, St Vincent's Hospital, Sydney, NSW 2010, Australia.
Jazyk:	angličtina
Zdroj:	The Biochemical journal [Biochem J] 2016 Sep 15; Vol. 473 (18), pp. 2763-82. Date of Electronic Publication: 2016 Jun 30.
DOI:	10.1042/BCJ20160541
Abstrakt:	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. (© 2016 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.)
Databáze:	MEDLINE
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