ERM protein family
| Ezrin/radixin/moesin family | |||||||||||
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The ERM protein family consists of three closely related proteins, ezrin,[2] radixin[3] and moesin.[4][5] 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.[6]
ERM proteins are highly conserved throughout evolution. More than 75% identity is observed in the N-terminal and the C-terminal of vertebrates (ezrin, radixin, moesin), Drosophila (dmoesin) and C. elegans (ERM-1) homologs.[7]
Structure
ERM molecules contain the following three domains:[5]
- The FERM domain is composed of three subdomains (F1, F2, F3) that are arranged as a cloverleaf.
- extended alpha-helical domain.
- charged C-terminal domain. This domain mediates the interaction with F-actin.
Ezrin, radixin and moesin also contain a polyproline region between the central helical and C-terminal domains.
Function
ERM proteins crosslink
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.[9]
Activation
ERM proteins are highly regulated proteins. They exist in two forms:[6][7]
- 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%[10]).
The current model for ERM protein activation is a two-step mechanism:[11]
- 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 localized in a highly conserved region of the C-terminal domain. The phosphate will stabilize the opening of the molecule.