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The structure and substrate specificity of human Cdk12/Cyclin K
CA. Bösken, L. Farnung, C. Hintermair, M. Merzel Schachter, K. Vogel-Bachmayr, D. Blazek, K. Anand, RP. Fisher, D. Eick, M. Geyer,
Language English Country England, Great Britain
Document type Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
NLK
Free Medical Journals
from 2010
PubMed Central
from 2012
Europe PubMed Central
from 2012
ProQuest Central
from 2010-01-01 to 2017-12-31
Medline Complete (EBSCOhost)
from 2012-11-01
Health & Medicine (ProQuest)
from 2010-01-01 to 2017-12-31
ROAD: Directory of Open Access Scholarly Resources
from 2010
Springer Nature OA/Free Journals
from 2010-12-01
Springer Nature - nature.com Journals - Fully Open Access
from 2010-12-01
PubMed
24662513
DOI
10.1038/ncomms4505
Knihovny.cz E-resources
- MeSH
- Cyclin-Dependent Kinases chemistry metabolism MeSH
- Cyclins chemistry metabolism MeSH
- Enzyme-Linked Immunosorbent Assay MeSH
- HeLa Cells MeSH
- Mass Spectrometry MeSH
- Immunoprecipitation MeSH
- Protein Conformation MeSH
- Crystallization MeSH
- Humans MeSH
- Models, Molecular * MeSH
- Multiprotein Complexes chemistry metabolism MeSH
- Substrate Specificity MeSH
- Blotting, Western MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Extramural MeSH
Phosphorylation of the RNA polymerase II C-terminal domain (CTD) by cyclin-dependent kinases is important for productive transcription. Here we determine the crystal structure of Cdk12/CycK and analyse its requirements for substrate recognition. Active Cdk12/CycK is arranged in an open conformation similar to that of Cdk9/CycT but different from those of cell cycle kinases. Cdk12 contains a C-terminal extension that folds onto the N- and C-terminal lobes thereby contacting the ATP ribose. The interaction is mediated by an HE motif followed by a polybasic cluster that is conserved in transcriptional CDKs. Cdk12/CycK showed the highest activity on a CTD substrate prephosphorylated at position Ser7, whereas the common Lys7 substitution was not recognized. Flavopiridol is most potent towards Cdk12 but was still 10-fold more potent towards Cdk9. T-loop phosphorylation of Cdk12 required coexpression with a Cdk-activating kinase. These results suggest the regulation of Pol II elongation by a relay of transcriptionally active CTD kinases.
References provided by Crossref.org
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