Elucidation of Short linear motif based interactions and dynamics of the ezrin, radixin, moesin and merlin FERM domains

Journal article


Muhammad Ali, Alisa Khramushin, Yadav, V., Ora Schueler-Furman and Ylva Ivarsson 2023. Elucidation of Short linear motif based interactions and dynamics of the ezrin, radixin, moesin and merlin FERM domains. Biochemistry. Vol 62 (Issue 11), p. 1594–1607. https://doi.org/10.1021/acs.biochem.3c00096
AuthorsMuhammad Ali, Alisa Khramushin, Yadav, V., Ora Schueler-Furman and Ylva Ivarsson
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.

KeywordsERM; Proteins; Screening; Interactomes
Year2023
JournalBiochemistry
Journal citationVol 62 (Issue 11), p. 1594–1607
PublisherACS Publications
ISSN0006-2960
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 statusPublished
Publication dates
Online24 May 2023
Online06 Jun 2023
Publication process dates
Deposited15 Jun 2023
Permalink -

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

  • 63
    total views
  • 0
    total downloads
  • 0
    views this month
  • 0
    downloads this month

Export as

Related outputs

Production of nano-protein particles in living cells
Yadav, V.K., Yadav, K. and Yang H. 2024. Production of nano-protein particles in living cells. Chemical Engineering Research and Design. 207, pp. 345-349. https://doi.org/10.1016/j.cherd.2024.06.007
Elucidation of Short Linear Motif-Based Interactions of the FERM Domains of Ezrin, Radixin, Moesin, and Merlin
Ali, M., Khramushin, A., Yadav, V.K., Schueler-Furman, O. and Ivarsson, Y. 2023. Elucidation of Short Linear Motif-Based Interactions of the FERM Domains of Ezrin, Radixin, Moesin, and Merlin. Biochemistry. pp. 1-14. https://doi.org/10.1021/acs.biochem.3c00096
Polypeptides that interact with peptide tags at loops or termini and uses thereof
Yadav, V. 2022. Polypeptides that interact with peptide tags at loops or termini and uses thereof. WO2022214795A1
Advanced downstream purification of high value biopharmaceuticals
Yadav, VK 2022. Advanced downstream purification of high value biopharmaceuticals. HVB/BBNet ECR Workshop.
Positive and negative effects of graphite flake and monolayer graphene oxide templates on protein crystallization
Lin, Z., Tian, W., Yadav, V. K. and Yang, H. 2022. Positive and negative effects of graphite flake and monolayer graphene oxide templates on protein crystallization. Particuology. pp. 1-8. https://doi.org/10.1016/j.partic.2022.10.014
Coupling to short linear motifs creates versatile PME-1 activities in PP2A holoenzyme demethylation and inhibition
Li, Y., Balakrishnan, Vijaya Kumar . K., Rowse, M., Wu, C, G., Bravos, A. P., Yadav, VK, Ivarsson, Y., Strack, S., Novikova, I. V. and Xing, Y. 2022. Coupling to short linear motifs creates versatile PME-1 activities in PP2A holoenzyme demethylation and inhibition. Elife. 11, pp. 1-26. https://doi.org/10.7554/eLife.79736
DogCatcher allows loop-friendly protein-protein ligation
Heeble, A. H., Yadav, VK, Ferla, M. P., Bauer, C. C., Chuntharpursat-Bon, C., Huang, J., Bon, R. S. and Howarth, M. 2022. DogCatcher allows loop-friendly protein-protein ligation. Cell Chemical Biology. 29 (2), p. 339–350. https://doi.org/10.1016/j.chembiol.2021.07.005
Systematic Discovery of Short Linear Motifs Decodes Calcineurin Phosphatase Signaling.
Yadav, V. 2020. Systematic Discovery of Short Linear Motifs Decodes Calcineurin Phosphatase Signaling. Molecular cell. Vol 79 (Issue 2), pp. 342-358. https://doi.org/10.1016/j.molcel.2020.06.029
Synthetic toolbox adapted from bacterial superglues to staple proteins in modular assemblies
Yadav, V. 2019. Synthetic toolbox adapted from bacterial superglues to staple proteins in modular assemblies. Protein Engineering II: from new new molecules to new processes. York, UK 15 - 17 Jul 2019 Fluidic Analytics.
Orthogonal toolbox of bacterial superglues for covalent interactions
Yadav, V. 2019. Orthogonal toolbox of bacterial superglues for covalent interactions. Synthetic Biology UK 2019. University of Warwick 09 - 10 Dec 2019 Biochemical society.
PP2A-B' holoenzyme substrate recognition, regulation and role in cytokinesis.
Yadav, V. 2017. PP2A-B' holoenzyme substrate recognition, regulation and role in cytokinesis. Cell discovery. Vol 3 (2017, Article: 17027). https://doi.org/10.1038/celldisc.2017.27
Discovery of short linear motif-mediated interactions through phage display of intrinsically disordered regions of the human proteome.
Yadav, V. 2016. Discovery of short linear motif-mediated interactions through phage display of intrinsically disordered regions of the human proteome. The FEBS journal. Vol 284 (Issue 3), pp. 485-498. https://doi.org/10.1111/febs.13995
Systematic discovery of Short Linear Motifs decodes hippo pathway signalling
Yadav, V. 2016. Systematic discovery of Short Linear Motifs decodes hippo pathway signalling. The modularity of signalling proteins and networks, EMBO workshop. Seefeld in Tirol, Austria 20 - 25 Sep 2016 EMBO Workshop.
Structural and binding studies of SAP-1 protein with heparin.
Yadav, V. 2014. Structural and binding studies of SAP-1 protein with heparin. Chemical biology & drug design. Vol 85 (Issue 3), pp. 404 - 410. https://doi.org/10.1111/cbdd.12420