9QCV
Cryo-EM structure of CAK-CDK2-cyclin A2 bound to AMP-PNP
Summary for 9QCV
| Entry DOI | 10.2210/pdb9qcv/pdb |
| EMDB information | 53027 |
| Descriptor | Cyclin-dependent kinase 2, Cyclin-A2, CDK-activating kinase assembly factor MAT1, ... (8 entities in total) |
| Functional Keywords | complex, cell cycle, kinase, transferase |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 5 |
| Total formula weight | 203682.47 |
| Authors | Cushing, V.I.,Greber, B.J.,McGeoch, A.J.S.,Feng, J. (deposition date: 2025-03-05, release date: 2025-10-15, Last modification date: 2025-12-10) |
| Primary citation | 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 Cited by 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. 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. PubMed: 41100585DOI: 10.1126/science.adw0053 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.5 Å) |
Structure validation
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