@misc{10481/29706,
year = {2013},
url = {http://hdl.handle.net/10481/29706},
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.},
organization = {This research was funded by grant BIO2005-04650 from the Spanish Ministry of Education and Science (MEC) and FQM-02838 from the Andalucia Regional Government.},
publisher = {Public Library of Science (PLOS)},
keywords = {Binding analysis},
keywords = {Crystal structure},
keywords = {Crystal structure refinement},
keywords = {Nuclear magnetic resonance},
keywords = {Phenylalanine},
keywords = {Protein interactions},
keywords = {Tyrosine},
keywords = {Ubiquitination},
title = {Distinct ubiquitin binding modes exhibited by SH3 domains: molecular determinants and functional implications},
author = {Ortega-Roldán, José Luis and Casares Atienza, Salvador and Ringkjøbing Jensen, Malene and Cárdenes, Nayra and Bravo, Jerónimo and Blackledge, Martin and Azuaga Fortes, Ana Isabel and Nuland, Nico A. J. van},
}