PDBsum entry 2mcn

Cell cycle/signaling protein

PDB id: 2mcn

Contents

Protein chains

57 a.a.

76 a.a.

PDB id:

2mcn

Name:

Cell cycle/signaling protein

Title:

Distinct ubiquitin binding modes exhibited by sh3 domains: molecular determinants and functional implications

Structure:

Cd2-associated protein. Chain: a. Fragment: sh3a domain (unp residues 2-58). Synonym: mesenchyme-to-epithelium transition protein with sh3 domains 1, mets-1. Engineered: yes. Ubiquitin. Chain: b. Fragment: unp residues 1-76.

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Gene: cd2ap, mets1. Expressed in: escherichia coli. Expression_system_taxid: 562. Homo sapiens. Human. Organism_taxid: 9606.

NMR struc:

10 models

Authors:

J.Ortega-Roldan,L.Salmon,A.Azuaga,M.Blackledge,N.Van Nuland

Key ref:

J.L.Ortega Roldan et al. (2013). Distinct ubiquitin binding modes exhibited by SH3 domains: molecular determinants and functional implications. Plos One, 8, e73018. PubMed id: 24039852 DOI: 10.1371/journal.pone.0073018

Date:

22-Aug-13 Release date: 05-Feb-14

Protein chain

Q9JLQ0  (CD2AP_MOUSE) -  CD2-associated protein from Mus musculus

Seq: 637 a.a.

Struc: 57 a.a.

Protein chain

P0CG48  (UBC_HUMAN) -  Polyubiquitin-C from Homo sapiens

Seq: 685 a.a.

Struc: 76 a.a.

Enzyme reactions

• Enzyme class: Chains A, B: E.C.?

DOI no: 10.1371/journal.pone.0073018

Plos One 8:e73018 (2013)

PubMed id: 24039852

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

J.L.Ortega Roldan, S.Casares, M.Ringkjøbing Jensen, N.Cárdenes, J.Bravo, M.Blackledge, A.I.Azuaga, N.A.van Nuland.

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.