2AST

Crystal structure of Skp1-Skp2-Cks1 in complex with a p27 peptide

2AST の概要

• エントリーDOI: 10.2210/pdb2ast/pdb
• 関連するPDBエントリー: 1FQV 2ASS
• 分子名称: S-phase kinase-associated protein 1A, S-phase kinase-associated protein 2, Cyclin-dependent kinases regulatory subunit 1, ... (6 entities in total)
• 機能のキーワード: scf-substrate complex, lrr, cell cycle, protein turnover complex, ligase-ligase inhibitor complex, ligase/ligase inhibitor
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Nucleus: P46527
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 65908.13

構造登録者

Hao, B.,Zhang, N.,Schulman, B.A.,Wu, G.,Pagano, M.,Pavletich, N.P. (登録日: 2005-08-24, 公開日: 2005-10-18, 最終更新日: 2024-10-30)

主引用文献

Hao, B.,Zheng, N.,Schulman, B.A.,Wu, G.,Miller, J.J.,Pagano, M.,Pavletich, N.P.
Structural Basis of the Cks1-Dependent Recognition of p27(Kip1) by the SCF(Skp2) Ubiquitin Ligase.
Mol.Cell, 20:9-19, 2005

PubMed Abstract: The ubiquitin-mediated proteolysis of the Cdk2 inhibitor p27(Kip1) plays a central role in cell cycle progression, and enhanced degradation of p27(Kip1) is associated with many common cancers. Proteolysis of p27(Kip1) is triggered by Thr187 phosphorylation, which leads to the binding of the SCF(Skp2) (Skp1-Cul1-Rbx1-Skp2) ubiquitin ligase complex. Unlike other known SCF substrates, p27(Kip1) ubiquitination also requires the accessory protein Cks1. The crystal structure of the Skp1-Skp2-Cks1 complex bound to a p27(Kip1) phosphopeptide shows that Cks1 binds to the leucine-rich repeat (LRR) domain and C-terminal tail of Skp2, whereas p27(Kip1) binds to both Cks1 and Skp2. The phosphorylated Thr187 side chain of p27(Kip1) is recognized by a Cks1 phosphate binding site, whereas the side chain of an invariant Glu185 inserts into the interface between Skp2 and Cks1, interacting with both. The structure and biochemical data support the proposed model that Cdk2-cyclin A contributes to the recruitment of p27(Kip1) to the SCF(Skp2)-Cks1 complex.

PubMed: 16209941
DOI: 10.1016/j.molcel.2005.09.003

実験手法

X-RAY DIFFRACTION (2.3 Å)