2OVQ

Structure of the Skp1-Fbw7-CyclinEdegC complex

2OVQ の概要

• エントリーDOI: 10.2210/pdb2ovq/pdb
• 関連するPDBエントリー: 2OVP 2OVR
• 分子名称: S-phase kinase-associated protein 1A, F-box/WD repeat protein 7, cyclinE C-terminal degron, ... (5 entities in total)
• 機能のキーワード: f-box; wd40 domains; double phosphorylation, transcription-cell cycle complex, transcription/cell cycle
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Isoform 1: Nucleus, nucleoplasm . Isoform 2: Cytoplasm . Isoform 3: Nucleus, nucleolus : Q969H0
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 69227.36

構造登録者

Hao, B.,Oehlmann, S.,Sowa, M.E.,Harper, J.W.,Pavletich, N.P. (登録日: 2007-02-14, 公開日: 2007-04-24, 最終更新日: 2024-11-13)

主引用文献

Hao, B.,Oehlmann, S.,Sowa, M.E.,Harper, J.W.,Pavletich, N.P.
Structure of a Fbw7-Skp1-Cyclin E Complex: Multisite-Phosphorylated Substrate Recognition by SCF Ubiquitin Ligases
Mol.Cell, 26:131-143, 2007

PubMed Abstract: The ubiquitin-mediated proteolysis of cyclin E plays a central role in cell-cycle progression, and cyclin E accumulation is a common event in cancer. Cyclin E degradation is triggered by multisite phosphorylation, which induces binding to the SCF(Fbw7) ubiquitin ligase complex. Structures of the Skp1-Fbw7 complex bound to cyclin E peptides identify a doubly phosphorylated pThr380/pSer384 cyclin E motif as an optimal, high-affinity degron and a singly phosphorylated pThr62 motif as a low-affinity one. Biochemical data indicate that the closely related yeast SCF(Cdc4) complex recognizes the multisite phosphorylated Sic1 substrate similarly and identify three doubly phosphorylated Sic1 degrons, each capable of high-affinity interactions with two Cdc4 phosphate binding sites. A model that explains the role of multiple cyclin E/Sic1 degrons is provided by the findings that Fbw7 and Cdc4 dimerize, that Fbw7 dimerization enhances the turnover of a weakly associated cyclin E in vivo, and that Cdc4 dimerization increases the rate and processivity of Sic1 ubiquitination in vitro.

PubMed: 17434132
DOI: 10.1016/j.molcel.2007.02.022

実験手法

X-RAY DIFFRACTION (2.6 Å)