4ec9
From Proteopedia
Crystal structure of full-length cdk9 in complex with cyclin t
Structural highlights
Function[CCNT1_HUMAN] Regulatory subunit of the cyclin-dependent kinase pair (CDK9/cyclin-T1) complex, also called positive transcription elongation factor B (P-TEFb), which is proposed to facilitate the transition from abortive to productive elongation by phosphorylating the CTD (carboxy-terminal domain) of the large subunit of RNA polymerase II (RNA Pol II). In case of HIV or SIV infections, binds to the transactivation domain of the viral nuclear transcriptional activator, Tat, thereby increasing Tat's affinity for the transactivating response RNA element (TAR RNA). Serves as an essential cofactor for Tat, by promoting RNA Pol II activation, allowing transcription of viral genes. Publication Abstract from PubMedCDK9, 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. The CDK9 tail determines the reaction pathway of positive transcription elongation factor b.,Baumli S, Hole AJ, Wang LZ, Noble ME, Endicott JA Structure. 2012 Oct 10;20(10):1788-95. doi: 10.1016/j.str.2012.08.011. Epub 2012 , Sep 6. PMID:22959624[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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