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The CDK9 Tail Determines the Reaction Pathway of Positive Transcription Elongation Factor b

Lookup NU author(s): Dr Sonja Baumli, Dr Alison Hole, Lan Wang, Professor Martin NobleORCiD, Professor Jane Endicott

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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.

Publication metadata

Author(s): Baumli S, Hole AJ, Wang LZ, Noble MEM, Endicott JA

Publication type: Article

Publication status: Published

Journal: Structure

Year: 2012

Volume: 20

Issue: 10

Pages: 1788-1795

Print publication date: 10/10/2012

ISSN (print): 0969-2126

ISSN (electronic): 1878-4186

Publisher: Cell Press

URL: http://dx.doi.org/10.1016/j.str.2012.08.011

DOI: 10.1016/j.str.2012.08.011

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