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 residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

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 contain an ERM d ...

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 to the plasma membrane. It is highly similar in sequence to both ezrin and moesin. The radixin gene has ...

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 Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a sp ...

, 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, 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 the protein is ...

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

Drosophila ''Drosophila'' () is a genus of flies, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or (less frequently) pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many speci ...

'' (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 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 ov ...

filaments with plasma membranes. They co-localize with

CD44 The CD44 antigen is a cell-surface glycoprotein involved in cell–cell interactions, cell adhesion and migration. In humans, the CD44 antigen is encoded by the ''CD44'' gene on chromosome 11. CD44 has been referred to as HCAM (homing cell adhes ...

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 microtubules 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 proteins activation is a two-steps mechanism: * First,

phosphatidylinositol 4,5-bisphosphate Phosphatidylinositol 4,5-bisphosphate or PtdIns(4,5)''P''2, also known simply as PIP2 or PI(4,5)P2, is a minor phospholipid component of cell membranes. PtdIns(4,5)''P''2 is enriched at the plasma membrane where it is a substrate for a number o ...

interaction at the plasma membrane induces a pre-opening of ERM molecule * Then, a not yet identified kinase phosphorylates a Threonine 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