2K6D: CIN85 Sh3-C domain in complex with ubiquitin

CIN85 is an adaptor protein linking the ubiquitin ligase Cbl and clathrin-binding proteins in clathrin-mediated receptor endocytosis. The SH3 domains of CIN85 bind to a proline-rich region of Cbl. Here we show that all three SH3 domains of CIN85 bind to ubiquitin. We also present a data-based structural model of the CIN85 SH3-C domain in complex with ubiquitin. In this complex, ubiquitin binds to the canonical interaction surface of the SH3 domain for proline-rich ligands and mimics the PPII helix, and we provide evidence that ubiquitin competes with these ligands for binding. We demonstrate that disruption of ubiquitin binding results in constitutive ubiquitination of CIN85 and an increased level of ubiquitination of EGFR in the absence of EGF stimulation. These results suggest that competition between Cbl and ubiquitin binding to CIN85 regulates Cbl function and EGFR endocytosis.
PDB ID: 2K6DDownload
MMDB ID: 66105
PDB Deposition Date: 2008/7/7
Updated in MMDB: 2008/09
Experimental Method:
solution nmr
Source Organism:
Similar Structures:
Biological Unit for 2K6D: dimeric; determined by author
Molecular Components in 2K6D
Label Count Molecule
Proteins (2 molecules)
SH3 Domain-containing Kinase-binding Protein 1(Gene symbol: SH3KBP1)
Molecule annotation
Molecule annotation
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Citing MMDB