The EBP50-moesin interaction involves a binding site regulated by direct masking on the FERM domain

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Casey M Finnerty1, David Chambers, Janet Ingraffea

  • 1Department of Molecular Biology and Genetics, Biotechnology Building, Cornell University, Ithaca, NY 14853, USA.

Journal of Cell Science
|March 17, 2004
PubMed

Insights

The ezrin-radixin-moesin (ERM) protein FERM domain binds EBP50 via an alpha-helix. This reveals a second binding site on the FERM domain for membrane proteins, crucial for ERM protein function.

Area of Science:

  • Biochemistry
  • Structural Biology
  • Cell Biology

Background:

  • The ezrin-radixin-moesin (ERM) protein family acts as a bridge between microfilaments and the cell membrane.
  • ERM proteins are activated and bind the scaffolding protein EBP50.
  • Understanding ERM protein interactions is key to cell structure and signaling.

Purpose of the Study:

  • To determine the structural basis of the interaction between the moesin FERM domain and EBP50.
  • To identify distinct binding sites on the ERM FERM domain for membrane-associated proteins.
  • To enable structure-based mutations for dissecting ERM protein function.

Main Methods:

  • X-ray diffraction analysis of the moesin FERM domain complexed with an EBP50 peptide at 3.5 A resolution.
  • Sequence and structural comparisons to analyze binding interfaces.
  • In vitro biochemical assays with mutated peptides and proteins to confirm binding interactions.

Main Results:

  • The N-terminal FERM domain of moesin binds an alpha-helical EBP50 peptide.
  • This binding occurs at the same site occupied by the inhibitory C-terminal tail in dormant moesin.
  • The FERM domain possesses two distinct ligand-binding sites, including the previously identified ICAM-2 site.

Conclusions:

  • The FERM domain of ERM proteins has at least two distinct binding sites for membrane-associated proteins.
  • The binding of EBP50 to the FERM domain involves an alpha-helical interaction.
  • This structural insight allows for the targeted mutation of specific binding sites to study ERM protein function.

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