Distinct ubiquitin binding modes exhibited by sh3 domains: molecular determinants and functional implications [unknown]

J. Ortega-Roldan, A. Azuaga, M. Blackledge, N. Van Nuland
2013 unpublished
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
more » ... 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. Citation: Ortega Roldan JL, Casares S, Ringkjøbing Jensen M, Cárdenes N, Bravo J, et al. (2013) Distinct Ubiquitin Binding Modes Exhibited by SH3 Domains: Molecular Determinants and Functional Implications. PLoS ONE 8(9): e73018.
doi:10.2210/pdb2lz6/pdb fatcat:oj7jsxhzlbbcnn4dx43wqywena