2MCN

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

Summary for 2MCN

• Entry DOI: 10.2210/pdb2mcn/pdb
• Related: 2LZ6
• NMR Information: BMRB: 19447
• Descriptor: CD2-associated protein, Ubiquitin (2 entities in total)
• Functional Keywords: cell cycle-signaling protein complex, cell cycle/signaling protein
• Biological source: Mus musculus (mouse); More
• Cellular location: Cytoplasm, cytoskeleton: Q9JLQ0; Ubiquitin: Cytoplasm : P0CG48
• Total number of polymer chains: 2
• Total formula weight: 15857.92

Authors

Ortega-Roldan, J.,Salmon, L.,Azuaga, A.,Blackledge, M.,Van Nuland, N. (deposition date: 2013-08-22, release date: 2014-02-05, Last modification date: 2024-05-15)

Primary citation

Ortega Roldan, J.L.,Casares, S.,Ringkjbing Jensen, M.,Cardenes, N.,Bravo, J.,Blackledge, M.,Azuaga, A.I.,van Nuland, N.A.
Distinct ubiquitin binding modes exhibited by SH3 domains: molecular determinants and functional implications.
Plos One, 8:e73018-e73018, 2013

PubMed 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.

PubMed: 24039852
DOI: 10.1371/journal.pone.0073018

Experimental method

SOLUTION NMR