{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Cushing VI"],"funding":["Cancer Research UK","Medical Research Council","Wellcome Trust"],"pagination":["911-917"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7618291"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["390(6776)"],"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 o"],"journal":["Science (New York, N.Y.)"],"pubmed_title":["Structural basis of T-loop-independent recognition and activation of CDKs by the CDK-activating kinase."],"pmcid":["PMC7618291"],"funding_grant_id":["28159","MR/V009354/1"],"pubmed_authors":["Cushing VI","Dan LM","McGeoch AJS","Feng J","Davey NE","Williams SL","Choudhary JS","Greber BJ","Roumeliotis TI"],"additional_accession":[]},"is_claimable":false,"name":"Structural basis of T-loop-independent recognition and activation of CDKs by the CDK-activating kinase.","description":"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 o","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Nov","modification":"2026-06-11T05:01:57.379Z","creation":"2026-06-11T03:08:15.758Z"},"accession":"S-EPMC7618291","cross_references":{"pubmed":["41100585"],"doi":["10.1126/science.adw0053"]}}