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

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

Author information

1
Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne NE2 4HH, UK. sbaumli@gmx.ch

Abstract

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.

PMID:
22959624
PMCID:
PMC3469819
DOI:
10.1016/j.str.2012.08.011
[Indexed for MEDLINE]
Free PMC Article
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