9I9K

Cryo-EM structure of CAK-CDK2 (determined in the presence of ADP-AlFx)

9I9K の概要

• エントリーDOI: 10.2210/pdb9i9k/pdb
• EMDBエントリー: 52761
• 分子名称: CDK-activating kinase assembly factor MAT1, Cyclin-H, Cyclin-dependent kinase 7, ... (7 entities in total)
• 機能のキーワード: complex, cell cycle, kinase, transferase
• 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: 154705.29

構造登録者

Cushing, V.I.,Greber, B.J.,McGeoch, A.J.S.,Feng, J. (登録日: 2025-02-06, 公開日: 2025-10-15, 最終更新日: 2025-12-10)

主引用文献

Cushing, V.I.,McGeoch, A.J.S.,Williams, S.L.,Roumeliotis, T.I.,Feng, J.,Dan, L.M.,Choudhary, J.S.,Davey, N.E.,Greber, B.J.
Structural basis of T-loop-independent recognition and activation of CDKs by the CDK-activating kinase.
Science, 390:911-917, 2025

PubMed Abstract: Cyclin-dependent kinases (CDKs) are prototypical regulators of the cell cycle. The CDK-activating kinase (CAK) acts as a master regulator of CDK activity by catalyzing the activating phosphorylation of CDKs on a conserved threonine residue within the regulatory T-loop. However, structural data illuminating the mechanism by which the CAK recognizes and activates CDKs have remained elusive. In this study, we determined high-resolution structures of the CAK in complex with CDK2 and CDK2-cyclin A2 by cryogenic electron microscopy. Our structures reveal a T-loop-independent kinase-kinase interface with contributions from both kinase lobes. Computational analysis and structures of the CAK in complex with CDK1-cyclin B1 and CDK11 indicate that these structures represent the general architecture of CAK-CDK complexes. These results advance our mechanistic understanding of cell cycle regulation and kinase signaling cascades.

PubMed: 41100585
DOI: 10.1126/science.adw0053

実験手法

ELECTRON MICROSCOPY (2.4 Å)