Interaction between the HIV-1 Protein Vpr and the Adenine Nucleotide Translocator
| Autor: | Sabbah, B, Druillennec, S., Morellet, N., Bouaziz, B, Kroemer, G., Roques, B.P., Sabbah, Emmanuelle, Bouaziz, S. |
|---|---|
| Přispěvatelé: | Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Ecosystèmes forestiers (UR EFNO), Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA), Institut Gustave Roussy (IGR), U 266, Institut National de la Santé et de la Recherche Médicale (INSERM), Institut d'électronique fondamentale (IEF), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Bouaziz, Serge, Écosystèmes forestiers (UR EFNO), Centre national du machinisme agricole, du génie rural, des eaux et forêts (CEMAGREF) |
| Jazyk: | angličtina |
| Rok vydání: | 2006 |
| Předmět: |
Models
Molecular T-Lymphocytes viruses Apoptosis Plasma protein binding MESH: Drug Design Biochemistry MESH: vpr Gene Products Human Immunodeficiency Virus Mice MESH: Protein Structure Tertiary Protein structure HIV Seropositivity Drug Discovery MESH: Animals MESH: Anti-HIV Agents 0303 health sciences biology [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry Molecular Biology/Structural Biology [q-bio.BM] Adenine nucleotide translocator 030302 biochemistry & molecular biology virus diseases vpr Gene Products Human Immunodeficiency Virus ANT MESH: Surface Plasmon Resonance Transmembrane domain [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry Molecular Biology/Biomolecules [q-bio.BM] Molecular Medicine MESH: Mitochondrial ADP ATP Translocases Intermembrane space MESH: Models Molecular Protein Binding MESH: Gene Products vpr Anti-HIV Agents [SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry Molecular Biology/Structural Biology [q-bio.BM] MESH: Mice Transgenic Transgene Mice Transgenic 03 medical and health sciences MESH: HIV Seropositivity Animals Humans MESH: Protein Binding MESH: Mice 030304 developmental biology Pharmacology MESH: Humans Gene Products vpr MESH: Apoptosis Organic Chemistry Surface Plasmon Resonance biochemical phenomena metabolism and nutrition In vitro Protein Structure Tertiary MESH: T-Lymphocytes Drug Design biology.protein Mitochondrial ADP ATP Translocases |
| Zdroj: | Chemical Biology Chemical Biology Drug Design, 2006, 67 (2), pp.145-154. ⟨10.1111/j.1747-0285.2006.00340.x⟩ |
| ISSN: | 1747-0277 |
| Popis: | International audience; The HIV-1 protein Vpr circulates in the serum of seropositive individuals and in the cerebrospinal fluid of AIDS patients with neurological disorders. Vpr triggers apoptosis of numerous cell types after extracellular addition, vpr gene transfer or in the context of viral infection. Moreover, in vivo, transgenic mice over-expressing Vpr have enhanced T lymphocytes apoptosis. In previous studies, we suggested that the Vpr apoptotic activities were because of its binding to the adenine nucleotide translocator (ANT), a mitochondrial ATP/ADP antiporter. To specify this interaction, fragments of both proteins were synthesized and used in biochemical and biophysical experiments. We demonstrate here that in vitro, the (27-51) and (71-82) Vpr peptides bind to a region encompassing the first ANT intermembrane space loop and part of its second and third transmembrane helices. Computational analysis using a docking program associated to dynamic simulations enabled us to construct a three-dimensional model of the Vpr-ANT complex. In this model, the N-terminus of Vpr plunges in the ANT cavity whereas the Vpr C-terminal extremity is located at the surface of the ANT allowing possible interactions with a third partner. These results could be used to design molecules acting as pro-apoptotic Vpr analogs or as apoptosis inhibitors preventing the Vpr-ANT interaction. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text