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

Area of Science:

• Biochemistry
• Structural Biology
• Cell Biology

Background:

• Ezrin is a key member of the ezrin-radixin-moesin (ERM) protein family, essential for linking the actin cytoskeleton to cell membranes.
• ERM proteins exist in dormant and active conformations, regulated by intramolecular interactions between their domains.

Purpose of the Study:

• To elucidate the structural basis of ezrin's activation mechanism.
• To determine the solution structures of ezrin monomers and dimers.

Main Methods:

• X-ray crystallography was used to determine the structures of the active FERM domain and the dormant FERM:C-terminal domain complex of human ezrin.
• Small-angle X-ray scattering (SAXS) was employed to analyze the solution structures of full-length ezrin monomers and dimers.
• Sequence alignment and structural modeling were utilized to investigate ERM protein evolution and dimer formation.

Main Results:

• Crystal structures revealed a bistable phenylalanine array in subdomain F3, mobile in the active form and locked in the dormant form, suggesting a role in activation and signaling.
• SAXS data showed ezrin monomers as globular with a helical coiled coil, while dimers adopted an elongated dumbbell shape.
• A conserved helical region supports a model of antiparallel coiled-coil dimers with domain-swapped FERM:C-terminal complexes, potentially enabling parallel actin binding.

Conclusions:

• The structural plasticity of ezrin, particularly the phenylalanine array and dimer formation, is critical for its function in linking the cytoskeleton to membranes.
• The proposed dimer model provides insights into how ERM proteins might interact with actin filaments, influencing cellular processes.