6ATH

Cdk2/cyclin A/p27-KID-deltaC

6ATH の概要

• エントリーDOI: 10.2210/pdb6ath/pdb
• 分子名称: Cyclin-dependent kinase 2, Cyclin-A2, Cyclin-dependent kinase inhibitor 1B, ... (5 entities in total)
• 機能のキーワード: inhibitor, complex, idp, cdk, cyclin, kinase, phosphortlation, transferase
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 72545.48

構造登録者

White, S.W.,Yun, M. (登録日: 2017-08-29, 公開日: 2018-09-12, 最終更新日: 2024-11-20)

主引用文献

Tsytlonok, M.,Sanabria, H.,Wang, Y.,Felekyan, S.,Hemmen, K.,Phillips, A.H.,Yun, M.K.,Waddell, M.B.,Park, C.G.,Vaithiyalingam, S.,Iconaru, L.,White, S.W.,Tompa, P.,Seidel, C.A.M.,Kriwacki, R.
Dynamic anticipation by Cdk2/Cyclin A-bound p27 mediates signal integration in cell cycle regulation.
Nat Commun, 10:1676-1676, 2019

PubMed Abstract: p27 is an intrinsically disordered protein (IDP) that inhibits cyclin-dependent kinase (Cdk)/cyclin complexes (e.g., Cdk2/cyclin A), causing cell cycle arrest. Cell division progresses when stably Cdk2/cyclin A-bound p27 is phosphorylated on one or two structurally occluded tyrosine residues and a distal threonine residue (T187), triggering degradation of p27. Here, using an integrated biophysical approach, we show that Cdk2/cyclin A-bound p27 samples lowly-populated conformations that provide access to the non-receptor tyrosine kinases, BCR-ABL and Src, which phosphorylate Y88 or Y88 and Y74, respectively, thereby promoting intra-assembly phosphorylation (of p27) on distal T187. Even when tightly bound to Cdk2/cyclin A, intrinsic flexibility enables p27 to integrate and process signaling inputs, and generate outputs including altered Cdk2 activity, p27 stability, and, ultimately, cell cycle progression. Intrinsic dynamics within multi-component assemblies may be a general mechanism of signaling by regulatory IDPs, which can be subverted in human disease.

PubMed: 30976006
DOI: 10.1038/s41467-019-09446-w

実験手法

X-RAY DIFFRACTION (1.82 Å)