The CDK9 tail determines the reaction pathway of positive transcription elongation factor b

Structure. 2012 Oct 10;20(10):1788-95. doi: 10.1016/j.str.2012.08.011. Epub 2012 Sep 6.


CDK9, the kinase of positive transcription elongation factor b (P-TEFb), stimulates transcription elongation by phosphorylating RNA polymerase II and transcription elongation factors. Using kinetic analysis of a human P-TEFb complex consisting of CDK9 and cyclin T, we show that the CDK9 C-terminal tail sequence is important for the catalytic mechanism and imposes an ordered binding of substrates and release of products. Crystallographic analysis of a CDK9/cyclin T complex in which the C-terminal tail partially blocks the ATP binding site reveals a possible reaction intermediate. Biochemical characterization of CDK9 mutants supports a model in which the CDK9 tail cycles through different conformational states. We propose that this mechanism is critical for the pattern of CTD Ser2 phosphorylation on actively transcribed genes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Substitution
  • Catalytic Domain
  • Crystallography, X-Ray
  • Cyclin T / chemistry*
  • Cyclin-Dependent Kinase 9 / antagonists & inhibitors
  • Cyclin-Dependent Kinase 9 / chemistry*
  • Cyclin-Dependent Kinase 9 / genetics
  • Dichlororibofuranosylbenzimidazole / chemistry
  • Humans
  • Kinetics
  • Models, Molecular
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Peptide Fragments / chemistry
  • Positive Transcriptional Elongation Factor B / chemistry
  • Protein Binding
  • Protein Kinase Inhibitors / chemistry


  • CCNT1 protein, human
  • Cyclin T
  • Peptide Fragments
  • Protein Kinase Inhibitors
  • Dichlororibofuranosylbenzimidazole
  • Positive Transcriptional Elongation Factor B
  • CDK9 protein, human
  • Cyclin-Dependent Kinase 9

Associated data

  • PDB/4EC8
  • PDB/4EC9