HIV-CYCTAT-COMPLEXES · Structural studies on the HIV/EIAV Encoded Transcriptional Activator Tat in complex with TAR and the cellular components, Cyclin T1 and Cdk9
FP6 — Marie Curie Actions (Human Resources and Mobility)
- Duration
- 2007-07-01 → 2009-06-30
- EU contribution
- €202,778
- Participants
- 1
- Scheme
- IIF
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Results in brief
Final Activity Report Summary - HIV-CYCTAT-COMPLEXES (Structural studies on the HIV/EIAV Encoded Transcriptional Activator Tat in complex with TAR and the cellular components, Cyclin T1 and Cdk9)
The replication of many retroviruses is mediated by a transcriptional activator protein, Tat, which activates RNA polymerase II at the level of transcription elongation. Tat interacts with Cyclin T1 of the positive transcription-elongation factor P-TEFb to recruit the transactivation-response TAR RNA, which acts as a promoter element in the transcribed 5¢ end of the viral long terminal repeat. Here we present the structure of the cyclin box domain of Cyclin T1 in complex with the Tat protein from the equine infectious anemia virus and its corresponding TAR RNA. The basic RNA-recognition motif of Tat adopts a helical structure whose flanking regions interact with a cyclin T-specific loop in the first cyclin box repeat. Together, both proteins coordinate the stem-loop structure of TAR. Our findings show that Tat binds to a surface on Cyclin T1 similar to where recognition motifs from substrate and inhibitor peptides were previously found to interact within Cdk-cyclin pairs.
Data: CORDIS, © European Union
Project objective
The human immunodeficiency virus (HIV) which is the retroviral causative agent of Acquired Immunodeficiency Syndrome (AIDS) has killed more than 20 million people.This proposal addresses on characterization of an important HIV-protein Tat ((transcriptional activator), which binds to transactivator response (TAR) RNA and cellular cofactors Cyclin T1 and Cdk9) involved in the transcriptional regulation of HIV replication.Inhibition of this complex formation could lead to much awaited antiviral drug. Thus, results from this project are expected to lead the development of the drug against HIV infection. The goal of this research proposal is the three-dimensional structure analysis of the Tat-TAR-Cyclin T1-Cdk9 complex of HIV and its relative Equine Immunodeficiency Virus (EIAV).As the project aims for an antiviral drug therapy to save millions of lives around the world, it will be followed-up by pharmaceutical companies to develop a drug against HIV infection. The main focus will be on expression, purification, crystallization, structure determination and finally identification of lead compound against HIV infection.The structural genomics methodology of the proposal fits very well with the actions envisaged in the FP6 programme that is combating the three poverty-linked infectious diseases (AIDS, malaria and tuberculosis), which have priority in terms of disease control at Union and international level.The state-of-art facilities and training at EMBL will not only assist the project, social and scientific community but will also benefit the applicant to become a trained independent researcher with complementary skills.The results from this project can be directly transferred to a competent European pharmaceutical company for the development of the drug.
Original text from CORDIS.
Participants
- EUROPEAN MOLECULAR BIOLOGY LABORATORY · HEIDELBERGCoordinatorGermany
Links
Data: CORDIS, © European Union