Mapping of domains on HIV envelope protein mediating association with calnexin and protein-disulfide isomerase
| Autor: | Emmanuel Fenouillet, Michel Khrestchatisky, Santiago Rivera, Marie-Jeanne Papandréou, Ian M. Jones, Régis Guieu, Rym Barbouche, Jacques Fantini |
|---|---|
| Přispěvatelé: | Neurobiologie des interactions cellulaires et neurophysiopathologie - NICN (NICN), Centre National de la Recherche Scientifique (CNRS)-Université de la Méditerranée - Aix-Marseille 2, CNRS FRE2738 (FRE2738), Hôpital de la Timone [CHU - APHM] (TIMONE), Centre de recherche en neurobiologie - neurophysiologie de Marseille (CRN2M), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), School of Biological Sciences [Reading], University of Reading (UOR), Université de la Méditerranée - Aix-Marseille 2-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Calnexin
viruses MESH: Cricetinae Plasma protein binding HIV Antibodies HIV Envelope Protein gp120 Biochemistry MESH: Peptide Mapping HIV Envelope Protein gp160 MESH: Recombinant Proteins Mice MESH: Protein Structure Tertiary MESH: HIV Envelope Protein gp120 Protein structure Cricetinae MESH: Animals Protein disulfide-isomerase chemistry.chemical_classification 0303 health sciences 030302 biochemistry & molecular biology virus diseases Recombinant Proteins 3. Good health Protein Structure and Folding Protein Binding inorganic chemicals Protein Disulfide-Isomerases Biology Peptide Mapping Cell Line 03 medical and health sciences Animals Humans MESH: Protein Binding MESH: Protein Disulfide-Isomerases Binding site [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry Molecular Biology/Biochemistry [q-bio.BM] Molecular Biology MESH: Calnexin MESH: Mice 030304 developmental biology MESH: Humans MESH: HIV Antibodies C-terminus Cell Biology HIV envelope protein MESH: HIV Envelope Protein gp160 Protein Structure Tertiary nervous system diseases MESH: Cell Line body regions chemistry Glycoprotein |
| Zdroj: | Journal of Biological Chemistry Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2010, 285 (18), pp.13788-96. ⟨10.1074/jbc.M109.066670⟩ Journal of Biological Chemistry, 2010, 285 (18), pp.13788-96. ⟨10.1074/jbc.M109.066670⟩ |
| ISSN: | 0021-9258 1083-351X |
| Popis: | International audience; The cell catalysts calnexin (CNX) and protein-disulfide isomerase (PDI) cooperate in establishing the disulfide bonding of the HIV envelope (Env) glycoprotein. Following HIV binding to lymphocytes, cell-surface PDI also reduces Env to induce the fusogenic conformation. We sought to define the contact points between Env and these catalysts to illustrate their potential as therapeutic targets. In lysates of Env-expressing cells, 15% of the gp160 precursor, but not gp120, coprecipitated with CNX, whereas only 0.25% of gp160 and gp120 coprecipitated with PDI. Under in vitro conditions, which mimic the Env/PDI interaction during virus/cell contact, PDI readily associated with Env. The domains of Env interacting in cellulo with CNX or in vitro with PDI were then determined using anti-Env antibodies whose binding site was occluded by CNX or PDI. Antibodies against domains V1/V2, C2, and the C terminus of V3 did not bind CNX-associated Env, whereas those against C1, V1/V2, and the CD4-binding domain did not react with PDI-associated Env. In addition, a mixture of the latter antibodies interfered with PDI-mediated Env reduction. Thus, Env interacts with intracellular CNX and extracellular PDI via discrete, largely nonoverlapping, regions. The sites of interaction explain the mode of action of compounds that target these two catalysts and may enable the design of further new competitive agents. |
| Databáze: | OpenAIRE |
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