A Model of N-Terminal Cyclin T1 Based on FRET Experiments. Issue 2 (2005)

• Record Type: Journal Article
• Authors: Pantano Pantano, Sergio Sergio; Marcello Marcello, Alessandro Alessandro; Sabò Sabò, Arianna Arianna; Ferrari Ferrari, Aldo Aldo; Pellegrini Pellegrini, Vittorio Vittorio; Beltram Beltram, Fabio Fabio; Giacca Giacca, Mauro Mauro; Carloni Carloni, Paolo Paolo
• Is Part Of: Journal of theoretical medicine. Volume 6:Issue 2(2005)
• Page Start: 73
• Page End: 79
• Publication Date: 2005
• Subjects: Cyclin T1 -- HIV-1 -- Tat -- FRET -- Comparative modelling -- P-TEFb; Biological models -- Periodicals; Biological systems -- Mathematical models -- Periodicals
• DOI: 10.1080/10273660500149430
• Languages: English
• ISSNs: 1027-3662

Abstract

Abstract : Human Cyclin T1 is the cyclin partner of kinase CDK9 in the positive transcription elongation factor b (P-TEFb). P-TEFb is recruited by Tat, the transactivator of the human immunodeficiency virus type 1 (HIV-1), to the viral promoter by direct interactions between Tat, Cyclin T1 and the cis -acting transactivation-responsive region (TAR) present at the 5′-end of each viral mRNA. At present, no structural data for Cyclin T1 are available. Here, we build a structural model of an N-terminus portion of Cyclin T1 (aa 27–263) based on the X-ray structure of Cyclin H. The model is compared with site directed mutagenesis data from the literature and validated by fluorescence resonance energy transfer (FRET) using Tat as a probe in living cells. This model provides a first step towards the structural characterization of the CDK9–CycT1–Tat-TAR complex, which is crucial for HIV-1 replication and may constitute a promising target for pharmaceutical intervention.