5VZT

Crystal structure of the Skp1-FBXO31 complex

5VZT の概要

• エントリーDOI: 10.2210/pdb5vzt/pdb
• 分子名称: S-phase kinase-associated protein 1, F-box only protein 31, ZINC ION, ... (6 entities in total)
• 機能のキーワード: ubiquitin ligase, cell cycle
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 146313.57

構造登録者

Li, Y.,Jin, K.,Hao, B. (登録日: 2017-05-29, 公開日: 2018-01-17, 最終更新日: 2024-03-13)

主引用文献

Li, Y.,Jin, K.,Bunker, E.,Zhang, X.,Luo, X.,Liu, X.,Hao, B.
Structural basis of the phosphorylation-independent recognition of cyclin D1 by the SCFFBXO31 ubiquitin ligase.
Proc. Natl. Acad. Sci. U.S.A., 115:319-324, 2018

PubMed Abstract: Ubiquitin-dependent proteolysis of cyclin D1 is associated with normal and tumor cell proliferation and survival. The SCF (Skp1-Cul1-Rbx1-FBXO31) ubiquitin ligase complex mediates genotoxic stress-induced cyclin D1 degradation. Previous studies have suggested that cyclin D1 levels are maintained at steady state by phosphorylation-dependent nuclear export and subsequent proteolysis in the cytoplasm. Here we present the crystal structures of the Skp1-FBXO31 complex alone and bound to a phosphorylated cyclin D1 C-terminal peptide. FBXO31 possesses a unique substrate-binding domain consisting of two β-barrel motifs, whereas cyclin D1 binds to FBXO31 by tucking its free C-terminal carboxylate tail into an open cavity of the C-terminal FBXO31 β-barrel. Biophysical and functional studies demonstrate that SCF is capable of recruiting and ubiquitinating cyclin D1 in a phosphorylation-independent manner. Our findings provide a conceptual framework for understanding the substrate specificity of the F-box protein FBXO31 and the mechanism of FBXO31-regulated cyclin D1 protein turnover.

PubMed: 29279382
DOI: 10.1073/pnas.1708677115

実験手法

X-RAY DIFFRACTION (2.7 Å)