The ERM protein family consists of three closely related

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

ezrin Ezrin also known as cytovillin or villin-2 is a protein that in humans is encoded by the ''EZR'' gene. Structure The N-terminus of ezrin contains a FERM domain which is further subdivided into three subdomains. The C-terminus contains an ...

radixin Radixin is a protein that in humans is encoded by the ''RDX'' gene. Radixin is a cytoskeletal protein that may be important in linking actin Actin is a family of globular multi-functional proteins that form microfilaments in the cytoske ...

and

moesin Moesin is a protein that in humans is encoded by the ''MSN'' gene. Moesin (for membrane-organizing extension spike protein) is a member of the ERM protein family which includes ezrin and radixin. ERM proteins appear to function as cross-linkers ...

. The three paralogs, ezrin, radixin and moesin, are present in vertebrates, whereas other species have only one ERM gene. Therefore, in vertebrates these paralogs likely arose by gene duplication. ERM proteins are highly conserved throughout evolution. More than 75% identity is observed in the N-terminal and the

C-terminal The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, carboxy tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When t ...

of vertebrates (ezrin, radixin, moesin), ''

Drosophila ''Drosophila'' (), from Ancient Greek δρόσος (''drósos''), meaning "dew", and φίλος (''phílos''), meaning "loving", is a genus of fly, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or p ...

'' (dmoesin) and '' C. elegans'' (ERM-1) homologs.

Structure

ERM molecules contain the following three domains: * N-terminal globular domain, also called FERM domain ( Band 4.1,

). The FERM domain allows ERM proteins to interact with integral proteins of the plasma membrane, or scaffolding proteins localized beneath the plasma membrane. The FERM domain is composed of three subdomains (F1, F2, F3) that are arranged as a cloverleaf. * extended alpha-helical domain. * charged

domain. This domain mediates the interaction with F-actin. Ezrin, radixin and moesin also contain a poly

proline Proline (symbol Pro or P) is an organic acid classed as a proteinogenic amino acid (used in the biosynthesis of proteins), although it does not contain the amino group but is rather a secondary amine. The secondary amine nitrogen is in the p ...

region between the central helical and C-terminal domains.

Function

ERM proteins crosslink

actin Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of ...

filaments with

plasma membrane The cell membrane (also known as the plasma membrane or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of a cell from the outside environment (the extr ...

s. They co-localize with CD44 at actin filament-plasma membrane interaction sites, associating with CD44 via their N-terminal domains and with actin filaments via their C-terminal domains. The ERM protein moesin directly binds to

microtubule Microtubules are polymers of tubulin that form part of the cytoskeleton and provide structure and shape to eukaryotic cells. Microtubules can be as long as 50 micrometres, as wide as 23 to 27 nanometer, nm and have an inner diameter bet ...

s via its N-terminal FERM domain ''in vitro'' and stabilizes microtubules at the cell cortex ''in vivo''. This interaction is required for specific ERM-dependent functions in mitosis.

Activation

ERM proteins are highly regulated proteins. They exist in two forms: * the FERM domain is able to interact with the F-actin binding site and this head-to-tail interaction maintains ERM proteins into a folded form; in this state, ERM proteins are ''inactive'' for the folding prevents either integral protein binding, or actin-binding. * if this head-to-tail interaction is disrupted, ERM proteins unfold, leading to an open and ''active'' conformation. In culture cells, ERM proteins mainly exhibit the folded conformation (about 80-85%). The current model for ERM protein activation is a two-step mechanism: * First, phosphatidylinositol 4,5-bisphosphate interaction at the plasma membrane induces a pre-opening of the ERM molecule. * Then, a not yet identified kinase phosphorylates a

threonine Threonine (symbol Thr or T) is an amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated −NH form when dissolved in water), a carboxyl group (which is in the deprotonated −COO− ...

localized in a highly conserved region of the C-terminal domain. The phosphate will stabilize the opening of the molecule.

References

{{Reflist, 2 Protein families Structural proteins Cytoskeleton