|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|
|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|
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.
|Alternate Journal||PLoS ONE|
|PubMed Central ID||PMC3770644|
Distinct ubiquitin binding modes exhibited by SH3 domains: molecular determinants and functional implications.