7LUO

N-terminus of Skp2 bound to Cyclin A

7LUO の概要

• エントリーDOI: 10.2210/pdb7luo/pdb
• 分子名称: S-phase kinase-associated protein 2,Cyclin-A2, Skp2 Motif 1 uncharacterized fragment 1, Skp2 Motif 1 uncharacterized fragment 2 (3 entities in total)
• 機能のキーワード: complex, cyclin, ligase, fusion, 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: 77183.49

構造登録者

Kelso, S.,Ceccarelli, D.F.,Sicheri, F. (登録日: 2021-02-22, 公開日: 2021-05-12, 最終更新日: 2023-10-18)

主引用文献

Kelso, S.,Orlicky, S.,Beenstock, J.,Ceccarelli, D.F.,Kurinov, I.,Gish, G.,Sicheri, F.
Bipartite binding of the N terminus of Skp2 to cyclin A.
Structure, 29:975-, 2021

PubMed Abstract: Skp2 and cyclin A are cell-cycle regulators that control the activity of CDK2. Cyclin A acts as an activator and substrate recruitment factor of CDK2, while Skp2 mediates the ubiquitination and subsequent destruction of the CDK inhibitor protein p27. The N terminus of Skp2 can interact directly with cyclin A but is not required for p27 ubiquitination. To gain insight into this poorly understood interaction, we have solved the 3.2 Å X-ray crystal structure of the N terminus of Skp2 bound to cyclin A. The structure reveals a bipartite mode of interaction with two motifs in Skp2 recognizing two discrete surfaces on cyclin A. The uncovered binding mechanism allows for a rationalization of the inhibitory effect of Skp2 on CDK2-cyclin A kinase activity toward the RxL motif containing substrates and raises the possibility that other intermolecular regulators and substrates may use similar non-canonical modes of interaction for cyclin targeting.

PubMed: 33989513
DOI: 10.1016/j.str.2021.04.011

実験手法

X-RAY DIFFRACTION (3.17 Å)