Journal of Theoretical Medicine
Volume 6 (2005), Issue 2, Pages 73-79
doi:10.1080/10273660500149430

A Model of N-Terminal Cyclin T1 Based on FRET Experiments

Sergio Pantano,1,5 Alessandro Marcello,2,3 Arianna Sabò,4 Aldo Ferrari,3 Vittorio Pellegrini,3 Fabio Beltram,3,4 Mauro Giacca,2,3,4 and Paolo Carloni1,2

1International School for Advanced Studies (ISAS) and INFM–DEMOCRITOS Modeling Center for Research in Atomistic Simulation, Via Beirut 2–4, 34014 Trieste, Italy
2International Center for Genetic Engineering and Biotechnology (ICGEB), Padriciano 99, 34012 Trieste, Italy
3National Enterprise for nanoScience and nanoTechnology–Istituto Nazionale di Fisica della Materia (NEST–INFM), Via della Faggiola 17, 56126 Pisa, Italy
4Scuola Normale Superiore, Piazza dei Cavalieri 7, 56100 Pisa, Italy
5Venetian Institute of Molecular Medicine (VIMM), Via Orus 2, 35129 Padua, Italy

Copyright © 2005 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.