The structure and substrate specificity of human Cdk12/Cyclin K

• DOI: 10.1038/ncomms4505
• Publication Date: 2014-03-24T14:04:25Z
• Authors: Christian A. Bösken; Lucas Farnung; Corinna Hintermair; Miriam Merzel Sch...; Karin Vogel-Bachmayr; Dalibor Blazek; Kanchan Anand; Robert P. Fisher; Dirk Eick; Matthias Geyer
• Keywords: RNA polymerase II; CTD; Transcription; C-terminus; Eukaryotic transcription

Phosphorylation of the RNA polymerase II C-terminal domain (CTD) by cyclin-dependent kinases is important for productive transcription. Here we determine crystal structure Cdk12/CycK and analyse its requirements substrate recognition. Active arranged in an open conformation similar to that Cdk9/CycT but different from those cell cycle kinases. Cdk12 contains a extension folds onto N- lobes thereby contacting ATP ribose. The interaction mediated HE motif followed polybasic cluster conserved transcriptional CDKs. showed highest activity on CTD prephosphorylated at position Ser7, whereas common Lys7 substitution was not recognized. Flavopiridol most potent towards still 10-fold more Cdk9. T-loop phosphorylation required coexpression with Cdk-activating kinase. These results suggest regulation Pol elongation relay transcriptionally active