Title | Distinct ubiquitin binding modes exhibited by SH3 domains: molecular determinants and functional implications. |
Publication Type | Journal Article |
Year of Publication | 2013 |
Authors | Roldan, J. L. Ortega, S. Casares, M. Ringkjøbi Jensen, N. Cárdenes, J. Bravo, M. Blackledge, A. I. Azuaga, and N. A. J. van Nuland |
Journal | PLoS One |
Volume | 8 |
Issue | 9 |
Pagination | e73018 |
Date Published | 2013 |
ISSN | 1932-6203 |
Keywords | Adaptor Proteins, Signal Transducing, Cytoskeletal Proteins, Models, Molecular, Mutation, Nuclear Magnetic Resonance, Biomolecular, Protein Binding, Protein Conformation, Protein Interaction Domains and Motifs, src Homology Domains, Ubiquitin |
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. |
DOI | 10.1371/journal.pone.0073018 |
Alternate Journal | PLoS ONE |
PubMed ID | 24039852 |
PubMed Central ID | PMC3770644 |
- Log in to post comments
- Google Scholar
- PubMed
- DOI