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Structural basis of T-loop-independent recognition and activation of CDKs by the CDK-activating kinase

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 catalysing 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 recognises and activates CDKs have remained elusive. Here, we determine high-resolution structures of the CAK in complex with CDK2 and CDK2-cyclin A 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 B 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 signalling cascades.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Graeme Benstead-Hume

LAB HEAD: Jyoti Choudhary

PROVIDER: PXD068021 | Pride | 2025-10-16

REPOSITORIES: Pride

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			Action	DRS
	iLab250-VC-Greber_01.raw	Raw
	iLab250-VC-Greber_02.raw	Raw
	iLab250-VC-Greber_03.raw	Raw
	iLab250-VC-Greber_04.raw	Raw
	iLab250-VC-Greber_05.raw	Raw

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