Details

Autor(en) / Beteiligte

• Ortega Roldan, Jose L
• Casares, Salvador
• Ringkjøbing Jensen, Malene
• Cárdenes, Nayra
• Bravo, Jerónimo
• Blackledge, Martin
• Azuaga, Ana I
• van Nuland, Nico A J
• Buday, Laszlo

Titel

Distinct ubiquitin binding modes exhibited by SH3 domains: molecular determinants and functional implications

Ist Teil von

• PloS one, 2013-09, Vol.8 (9), p.e73018-e73018

Ort / Verlag

United States: Public Library of Science

Erscheinungsjahr

2013

Link zum Volltext

Quelle

Electronic Journals Library - Freely accessible e-journals

Beschreibungen/Notizen

• 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.