The CDK9 Tail Determines the Reaction Pathway of Positive Transcription Elongation Factor b
Copyright policy )The CDK9 Tail Determines the Reaction Pathway of Positive Transcription Elongation Factor b
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.
- Institute of Cancer Research United Kingdom
- Newcastle University United Kingdom
Models, Molecular, Cyclin T, Molecular Sequence Data, Crystallography, X-Ray, Cyclin-Dependent Kinase 9, Article, Peptide Fragments, Kinetics, Amino Acid Substitution, Structural Biology, Catalytic Domain, Mutagenesis, Site-Directed, Humans, Positive Transcriptional Elongation Factor B, Amino Acid Sequence, Molecular Biology, Protein Kinase Inhibitors, Dichlororibofuranosylbenzimidazole, Protein Binding
Models, Molecular, Cyclin T, Molecular Sequence Data, Crystallography, X-Ray, Cyclin-Dependent Kinase 9, Article, Peptide Fragments, Kinetics, Amino Acid Substitution, Structural Biology, Catalytic Domain, Mutagenesis, Site-Directed, Humans, Positive Transcriptional Elongation Factor B, Amino Acid Sequence, Molecular Biology, Protein Kinase Inhibitors, Dichlororibofuranosylbenzimidazole, Protein Binding
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