2K6D

CIN85 Sh3-C domain in complex with ubiquitin

Summary for 2K6D

• Entry DOI: 10.2210/pdb2k6d/pdb
• NMR Information: BMRB: 15866
• Descriptor: SH3 domain-containing kinase-binding protein 1, Ubiquitin (2 entities in total)
• Functional Keywords: cin85, sh3 domain, ubiquitin, alternative splicing, apoptosis, cell junction, coiled coil, cytoplasm, cytoplasmic vesicle, cytoskeleton, endocytosis, membrane, phosphoprotein, polymorphism, sh3-binding, synapse, synaptosome, ubl conjugation, nucleus, sh3 domain-ubiquitin complex, sh3 domain/ubiquitin
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 15774.01

Authors

Forman-Kay, J.,Bezsonova, I. (deposition date: 2008-07-07, release date: 2008-08-19, Last modification date: 2024-05-01)

Primary citation

Bezsonova, I.,Bruce, M.C.,Wiesner, S.,Lin, H.,Rotin, D.,Forman-Kay, J.D.
Interactions between the three CIN85 SH3 domains and ubiquitin: implications for CIN85 ubiquitination.
Biochemistry, 47:8937-8949, 2008

PubMed Abstract: 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.

PubMed: 18680311
DOI: 10.1021/bi800439t

Experimental method

SOLUTION NMR