PXD068021-1

PXD068021 is an original dataset announced via ProteomeXchange.

Title	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 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.
HostingRepository	PRIDE
AnnounceDate	2025-10-16
AnnouncementXML	Submission_2025-10-16_06:23:01.119.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Graeme Benstead-Hume
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Ascend

Revision	Datetime	Status	ChangeLog Entry
0	2025-09-03 03:50:03	ID requested
⏵ 1	2025-10-16 06:23:01	announced

Dataset with its publication pending

submitter keyword: T-loop-independent recognition,CDK-activating kinase

Jyoti Choudhary
contact affiliation	ICR. Functional Proteomics
contact email	jyoti.choudhary@icr.ac.uk
lab head
Graeme Benstead-Hume
contact affiliation	ICR
contact email	ghume@icr.ac.uk
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/10/PXD068021

PRIDE project URI

• PRIDE
  1. PXD068021
     1. Label: PRIDE project
     2. Name: Structural basis of T-loop-independent recognition and activation of CDKs by the CDK-activating kinase