2mcn
Distinct ubiquitin binding modes exhibited by SH3 domains: molecular determinants and functional implicationsDistinct ubiquitin binding modes exhibited by SH3 domains: molecular determinants and functional implications
Structural highlights
FunctionCD2AP_MOUSE Required for cytokinesis (By similarity). Seems to act as an adapter protein between membrane proteins and the actin cytoskeleton. May play a role in receptor clustering and cytoskeletal polarity in the junction between T-cell and antigen-presenting cell. May anchor the podocyte slit diaphragm to the actin cytoskeleton in renal glomerolus.[1] Publication Abstract from PubMedSH3 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. Distinct Ubiquitin Binding Modes Exhibited by SH3 Domains: Molecular Determinants and Functional Implications.,Ortega Roldan JL, Casares S, Ringkjobing Jensen M, Cardenes N, Bravo J, Blackledge M, Azuaga AI, van Nuland NA PLoS One. 2013 Sep 11;8(9):e73018. doi: 10.1371/journal.pone.0073018. PMID:24039852[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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