该课题组研究人员通过低温电子显微镜确定了CAK与CDK2和CDK2-cyclin A2复合物的高分辨率结构。它们的结构揭示了一个不依赖于t环的激酶-激酶界面，并有两个激酶叶的贡献。计算分析和CAK与CDK1-cyclin B1和CDK11复合物的结构表明，这些结构代表了CAK-CDK复合物的一般结构。这些结果促进了他们对细胞周期调控和激酶信号级联的机制理解。
据介绍，细胞周期蛋白依赖性激酶（CDKs）是细胞周期的典型调节因子。CDK活化激酶（CAK）作为CDK活性的主要调节剂，通过在调节T环内的保守苏氨酸残基上催化CDK的活化磷酸化。然而，阐明CAK识别和激活CDKs的机制的结构数据仍然缺乏。
附：英文原文
Title: Structural basis of T-loop–independent recognition and activation of CDKs by the CDK-activating kinase
Author: Victoria I. Cushing, Amy J. S. McGeoch, Sophie L. Williams, Theodoros I. Roumeliotis, Junjie Feng, Lucy M. Dan, Jyoti S. Choudhary, Norman E. Davey, Basil J. Greber
Issue&Volume: 2025-10-16
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. Here, we determine 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 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.
DOI: adw0053
Source: https://www.science.org/doi/10.1126/science.adw0053