A Model of N-Terminal Cyclin T1 Based on FRET Experiments-Reference-Cited by-同舟云学术

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

Published:2005 Issue:2 Volume:6 Page:73-79
ISSN:1027-3662
Container-title:Journal of Theoretical Medicine
language:en
Short-container-title:Journal of Theoretical Medicine

Author:

Pantano Sergio¹²,Marcello Alessandro³⁴,Sabò Arianna⁵,Ferrari Aldo⁴,Pellegrini Vittorio⁴,Beltram Fabio⁴⁵,Giacca Mauro³⁴⁵,Carloni Paolo¹³

Affiliation:

1. International School for Advanced Studies (ISAS) and INFM–DEMOCRITOS Modeling Center for Research in Atomistic Simulation, Via Beirut 2–4, 34014 Trieste, Italy

2. Venetian Institute of Molecular Medicine (VIMM), Via Orus 2, 35129 Padua, Italy

3. International Center for Genetic Engineering and Biotechnology (ICGEB), Padriciano 99, 34012 Trieste, Italy

4. National Enterprise for nanoScience and nanoTechnology–Istituto Nazionale di Fisica della Materia (NEST–INFM), Via della Faggiola 17, 56126 Pisa, Italy

5. Scuola Normale Superiore, Piazza dei Cavalieri 7, 56100 Pisa, Italy

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 thecis-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.

Funder

Istituto Superiore di Sanità

Publisher

Hindawi Limited

Subject

General Biochemistry, Genetics and Molecular Biology

Link

http://downloads.hindawi.com/journals/cmmm/2005/272839.pdf

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