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Distinct Ubiquitin Binding Modes Exhibited by SH3 Domains: Molecular Determinants and Functional Implications

Ortega-Roldan, Jose L., Casares, Salvador, Ringkjøbing Jensen, Malene, Cárdenes, Nayra, Bravo, Jerónimo, Blackledge, Martin, Azuaga, Ana I., van Nuland, Nico A. J. (2013) Distinct Ubiquitin Binding Modes Exhibited by SH3 Domains: Molecular Determinants and Functional Implications. PLoS ONE, 8 (9). e73018. ISSN 1932-6203. (doi:10.1371/journal.pone.0073018) (KAR id:62500)

Abstract

SH3 domains constitute a new type of ubiquitin-binding domains. We previously showed that the third SH3 domain (SH3-C) of CD2AP binds ubiquitin in an alternative orientation. We have determined the structure of the complex between first CD2AP SH3 domain and ubiquitin and performed a structural and mutational analysis to decipher the determinants of the SH3-C binding mode to ubiquitin. We found that the Phe-to-Tyr mutation in CD2AP and in the homologous CIN85 SH3-C domain does not abrogate ubiquitin binding, in contrast to previous hypothesis and our findings for the first two CD2AP SH3 domains. The similar alternative binding mode of the SH3-C domains of these related adaptor proteins is characterised by a higher affinity to C-terminal extended ubiquitin molecules. We conclude that CD2AP/CIN85 SH3-C domain interaction with ubiquitin constitutes a new ubiquitin-binding mode involved in a different cellular function and thus changes the previously established mechanism of EGF-dependent CD2AP/CIN85 mono-ubiquitination.

Item Type: Article
DOI/Identification number: 10.1371/journal.pone.0073018
Divisions: Divisions > Division of Natural Sciences > Biosciences
Depositing User: Jose Ortega Roldan
Date Deposited: 31 Jul 2017 14:13 UTC
Last Modified: 16 Nov 2021 10:24 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/62500 (The current URI for this page, for reference purposes)

University of Kent Author Information

Ortega-Roldan, Jose L..

Creator's ORCID: https://orcid.org/0000-0002-6316-4390
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