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| Title | Cryo-EM structures of the CDK11-cyclin L-SAP30BP complex reveal mechanisms of CDK11 regulation. |
|---|---|
| Journal, issue, pages | Nat Commun, Year 2026 |
| Publish date | Apr 25, 2026 |
Authors | Amy J S McGeoch / Victoria I Cushing / Theodoros I Roumeliotis / Nora B Cronin / Stephen J Hearnshaw / Jyoti S Choudhary / Claudio Alfieri / Basil J Greber / ![]() |
| PubMed Abstract | The cyclin-dependent kinase CDK11 functions in transcription, mitotic progression, and mRNA splicing. Specifically, spliceosome activation during the B to B transition depends on phosphorylation of ...The cyclin-dependent kinase CDK11 functions in transcription, mitotic progression, and mRNA splicing. Specifically, spliceosome activation during the B to B 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 that promote complex assembly. Destabilisation of cyclin L2 in the absence of SAP30BP suggests that these principles are applicable to all CDK11-cyclin L complexes. Furthermore, we identify a pseudo-substrate sequence near the CDK11 C-terminus and provide evidence for a role of this segment in CDK11 auto-regulation. Finally, the structure of the CDK11-cyclin L-SAP30BP complex bound to the clinical high-affinity CDK11 inhibitor OTS964 and a comparison to OTS964-bound off-target complexes provide insight into the mechanism of OTS964 selectivity and specificity. |
External links | Nat Commun / PubMed:42034640 |
| Methods | EM (single particle) |
| Resolution | 2.3 - 2.5 Å |
| Structure data | EMDB-53204, PDB-9qjj: EMDB-53205, PDB-9qjn: EMDB-53221, PDB-9qkt: EMDB-53224, PDB-9qkz: |
| Chemicals | ![]() ChemComp-NK3: ![]() ChemComp-HOH: ![]() ChemComp-ANP: ![]() ChemComp-MG: |
| Source |
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Keywords | CELL CYCLE / kinase / cyclin-dependent kinase / inhibitor / SPLICING / transcription / molecular complex |
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homo sapiens (human)
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