Specificite et structures secondaires des toxines de scorpions actives sur les insectes

SIGLEINIST T 71145 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

Etudes structurales et immunologiques de la protéine Tat du VIH-1

AIX-MARSEILLE2-BU Sci.Luminy (130552106) / SudocSudocFranceF

Approches thérapeutiques ciblant la protéine Tat du VIH-1 (Synthèse chimique de Tat et développement d'un antiviral et d'un vaccin)

AIX-MARSEILLE2-BU Sci.Luminy (130552106) / SudocSudocFranceF

Nouvelles approches thérapeutiques anti-HIV-1 (Elaboration et optimisation d'un nouvel agent anti rétroviral et développement d'un vaccin anti VIH)

AIX-MARSEILLE2-BU Sci.Luminy (130552106) / SudocSudocFranceF

Circular dichroism and molecular modeling yield a structure for the complex of human immunodeficiency virus type 1 trans-activation response RNA and the binding region of Tat, the trans-acting transcriptional activator

Transcription in the human immunodeficiency virus type 1 (HIV-1) retrovirus is regulated by binding the viral Tat protein (trans-acting transcriptional activator) to the trans-activation response (TAR) RNA sequence. Here, vacuum UV circular dichroism (VUV-CD) is used to study the structure of TAR and its complex with two peptide fragments that are important for Tat binding to TAR. The VUV-CD spectrum of TAR is typical of A-form RNA and is minimally perturbed when bound to either the short or the long Tat peptide. The CD spectra ofthe complexes indicate an extended structure in the argnine-rich region of Tat from amino acid residue 47 through residue 58 and a short a-helix within the adjacent 59-72 region. Models of TAR and its peptide complexes are constructed to integrate these spectroscopic results with current biochemical data. The model suggests that (i) the arginine-rich 49-58 region is primarily responsible for electrostatic interactions with the phosphates of the RNA, (ii) the arginine side chains can additionally interact with substituent groups of the nucleotide bases to confer base recognition in the complex, (iii) the recognition of uracil-23 in TAR is facilitated by the peptide backbone, and (iv) the glutamine-rich face of an a-helix within the 59-72 region pairs to bases UGG at nucleotide positions 31-33 in the TAR loop and thus provides an additional motif in the Tat trans-activating protein to recognize TAR RNA

Relations structure-fonction et propriétés immunologiques de la protéine Tat du VIH-1

HIV-1 induces the apoptosis of CD4+ T cells through multiple pathways. One such is by the HIV-1 Tat protein, which is secreted by virally infected cells and taken up by uninfected cells. Tat is expressed very early in the virus life cycle and plays a critical role in the transcription of HIV. We show that Tat proteins from patients with rapid disease progresion have greater trans-activational and apoptotic activities than from patients with slower rates of progression. The glutamine rich region of Tat appears to be implicated in these activities. The critical role of Tat in immunodeficiency makes Tat a good candidate for a component in an HIV-1 vaccine. The study of the antibodies raised by Tat shows the importance of using a full length protein. Furthermore, macaques vaccinated with Tat Oyi and challenged with SHIV showedAIX-MARSEILLE2-BU Sci.Luminy (130552106) / SudocSudocFranceF