Elucidation of Short linear motif based interactions and dynamics of the ezrin, radixin, moesin and merlin FERM domains
Journal article
Authors | Muhammad Ali, Alisa Khramushin, Yadav, V., Ora Schueler-Furman and Ylva Ivarsson |
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Abstract | The ERM (ezrin, radixin, and moesin) family of proteins and the related protein merlin participate in scaffolding and signaling events at the cell cortex. The proteins share an N-terminal FERM [band four-point-one (4.1) ERM] domain composed of three subdomains (F1, F2, and F3) with binding sites for short linear peptide motifs. By screening the FERM domains of the ERMs and merlin against a phage library that displays peptides representing the intrinsically disordered regions of the human proteome, we identified a large number of novel ligands. We determined the affinities for the ERM and merlin FERM domains interacting with 18 peptides and validated interactions with full-length proteins through pull-down experiments. The majority of the peptides contained an apparent Yx[FILV] motif; others show alternative motifs. We defined distinct binding sites for two types of similar but distinct binding motifs (YxV and FYDF) using a combination of Rosetta FlexPepDock computational peptide docking protocols and mutational analysis. We provide a detailed molecular understanding of how the two types of peptides with distinct motifs bind to different sites on the moesin FERM phosphotyrosine binding-like subdomain and uncover interdependencies between the different types of ligands. The study expands the motif-based interactomes of the ERMs and merlin and suggests that the FERM domain acts as a switchable interaction hub. |
Keywords | ERM; Proteins; Screening; Interactomes |
Year | 2023 |
Journal | Biochemistry |
Journal citation | Vol 62 (Issue 11), p. 1594–1607 |
Publisher | ACS Publications |
ISSN | 0006-2960 |
1520-4995 | |
Digital Object Identifier (DOI) | https://doi.org/10.1021/acs.biochem.3c00096 |
Web address (URL) | https://pubs.acs.org/doi/10.1021/acs.biochem.3c00096 |
https://pubmed.ncbi.nlm.nih.gov/37224425/ | |
Output status | Published |
Publication dates | |
Online | 24 May 2023 |
Online | 06 Jun 2023 |
Publication process dates | |
Deposited | 15 Jun 2023 |
https://repository.derby.ac.uk/item/9z4xz/elucidation-of-short-linear-motif-based-interactions-and-dynamics-of-the-ezrin-radixin-moesin-and-merlin-ferm-domains
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