PXD060582

PXD060582 is an original dataset announced via ProteomeXchange.

Title	Cryo-EM structure of the CDK11-cyclin L-SAP30BP complex reveals mechanisms of CDK11 regulation
Description	The cyclin-dependent kinase CDK11 functions in transcription, mitotic progression, and mRNA splicing. Specifically, spliceosome activation during the B to Bact transition depends on phosphorylation of the U2 snRNP component SF3B1 by the CDK11-cyclin L-SAP30BP complex. Here, we present the structure of this spliceosome-activating CDK-cyclin complex, determined by cryogenic electron microscopy at 2.3 Å resolution. Our structure and biochemical experiments show that SAP30BP forms extensive interactions with cyclin L2, thereby stabilising it, and forms critical interactions with the C-terminal kinase lobe of CDK11. Destabilisation of cyclin L2 in the absence of SAP30BP suggests that these principles are applicable to all CDK11-cyclin L complexes. The structure of the CDK11-cyclin L2-SAP30BP complex bound to the inhibitor OTS964, a clinical, non-covalent, high-affinity CDK11 inhibitor and a comparison to OTS964-bound off-target complexes provide insight into the mechanism of OTS964 selectivity and specificity.
HostingRepository	PRIDE
AnnounceDate	2026-03-24
AnnouncementXML	Submission_2026-03-24_07:09:19.867.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	phosphorylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Ascend

Revision	Datetime	Status	ChangeLog Entry
0	2025-02-07 04:10:27	ID requested
⏵ 1	2026-03-24 07:09:20	announced

Dataset with its publication pending

submitter keyword: CDK11-cyclin, L-SAP30BP

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/2026/03/PXD060582

PRIDE project URI

• PRIDE
  1. PXD060582
     1. Label: PRIDE project
     2. Name: Cryo-EM structure of the CDK11-cyclin L-SAP30BP complex reveals mechanisms of CDK11 regulation