2K6D

CIN85 Sh3-C domain in complex with ubiquitin

2K6D の概要

• エントリーDOI: 10.2210/pdb2k6d/pdb
• NMR情報: BMRB: 15866
• 分子名称: SH3 domain-containing kinase-binding protein 1, Ubiquitin (2 entities in total)
• 機能のキーワード: 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
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 15774.01

構造登録者

Forman-Kay, J.,Bezsonova, I. (登録日: 2008-07-07, 公開日: 2008-08-19, 最終更新日: 2024-05-01)

主引用文献

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

実験手法

SOLUTION NMR