Abstract
The merlin-ERM (ezrin, radixin, moesin) family of proteins plays a central role in linking the cellular membranes to the cortical actin cytoskeleton. Merlin regulates contact inhibition and is an integral part of cell–cell junctions, while ERM proteins, ezrin, radixin and moesin, assist in the formation and maintenance of specialized plasma membrane structures and membrane vesicle structures. These two protein families share a common evolutionary history, having arisen and separated via gene duplication near the origin of metazoa. During approximately 0.5 billion years of evolution, the merlin and ERM family proteins have maintained both sequence and structural conservation to an extraordinary level. Comparing crystal structures of merlin-ERM proteins and their complexes, a picture emerges of the merlin-ERM proteins acting as switchable interaction hubs, assembling protein complexes on cellular membranes and linking them to the actin cytoskeleton. Given the high level of structural conservation between the merlin and ERM family proteins we speculate that they may function together.
Highlights
The paralogous proteins merlin and the ERMs—a group of proteins comprised of ezrin, radixin and moesin provide an interesting platform on which to study the evolution, divergence and acquisition of functional differences in a family of highly similar and highly conserved proteins
Model the T567D ezrin layer as a lateral assembly of open conformation, extended ezrin monomers with the FERM domain bound to the membrane and the C-Terminal Domain (CTD) bound to F-actin [96]
There is still a lot we do not know about the structure of merlin-ERM proteins and how structure dictates function
Summary
The paralogous proteins merlin ( called neurofibromatosis type 2 tumor suppressor, NF2 or schwannomin) and the ERMs—a group of proteins comprised of ezrin ( called cytovillin, villin-2 and p81), radixin and moesin (an acronym for membrane-organizing extension spike protein) provide an interesting platform on which to study the evolution, divergence and acquisition of functional differences in a family of highly similar and highly conserved proteins. Merlin is required for the formation of many membrane structures; it interacts with various signaling pathways not just proximal to the membrane but in the cytoplasm and nucleus as well. As these proteins have nearly identical tertiary structures, subtle differences in how each merlin-ERM member interacts with other proteins and how they mediate control over numerous pathways seems to be the driver behind their functional differentiation. Our perspective is that of structural biologists who follow the evolution of the merlin-ERM family from its emergence, which is synchronous to the appearance of metazoa
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