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

Ortega Roldan, JL and Casares, S and Ringkjøbing Jensen, M and Cárdenes, N and Bravo, J and Blackledge, M and Azuaga, AI and Van Nuland, NAJ (2013) Distinct ubiquitin binding modes exhibited by SH3 domains: Molecular determinants and functional implications. PLoS ONE, 8 (9).

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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. © 2013 Ortega Roldan et al.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Ortega Roldan, JL
Casares, S
Ringkjøbing Jensen, M
Cárdenes, N
Bravo, J
Blackledge, M
Azuaga, AI
Van Nuland, NAJ
Centers: Other Centers, Institutes, or Units > Vascular Medicine Institute
Date: 11 September 2013
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 8
Number: 9
DOI or Unique Handle: 10.1371/journal.pone.0073018
Refereed: Yes
Date Deposited: 17 Oct 2013 15:29
Last Modified: 02 Feb 2019 13:58
URI: http://d-scholarship.pitt.edu/id/eprint/19830

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