51. Rabies virus glycoprotein can fold in two alternative, antigenically distinct conformations depending on membrane-anchor type
- Author
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Antoine P. Maillard, Yves Gaudin, Pathogenèse bactérienne et réponses cellulaires (PBRC), Biologie du Cancer et de l'Infection (BCI ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Intégrative de la Cellule (I2BC), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)
- Subjects
Protein Folding ,Protein Conformation ,[SDV]Life Sciences [q-bio] ,Fluorescent Antibody Technique ,MESH: Amino Acid Sequence ,Antibodies, Viral ,Endoplasmic Reticulum ,MESH: Antibodies, Monoclonal ,Epitopes ,Protein structure ,MESH: Protein Conformation ,Viral Envelope Proteins ,Native state ,MESH: Animals ,Antigens, Viral ,Peptide sequence ,MESH: Fluorescent Antibody Technique ,Recombination, Genetic ,chemistry.chemical_classification ,0303 health sciences ,030302 biochemistry & molecular biology ,Antibodies, Monoclonal ,MESH: Rabies virus ,Transmembrane domain ,Ectodomain ,Electrophoresis, Polyacrylamide Gel ,Protein folding ,MESH: Recombination, Genetic ,MESH: Antigens, Viral ,MESH: Epitopes ,MESH: Mutation ,MESH: Protein Folding ,Molecular Sequence Data ,MESH: Glycoproteins ,MESH: Sequence Alignment ,Biology ,Cell Line ,03 medical and health sciences ,MESH: Endoplasmic Reticulum ,Virology ,Animals ,Amino Acid Sequence ,Glycoproteins ,030304 developmental biology ,MESH: Molecular Sequence Data ,Lipid bilayer fusion ,MESH: Cell Line ,chemistry ,Rabies virus ,MESH: Viral Envelope Proteins ,Mutation ,Glycoprotein ,Sequence Alignment ,MESH: Antibodies, Viral ,MESH: Electrophoresis, Polyacrylamide Gel - Abstract
Rabies virus glycoprotein (G) is a trimeric type I transmembrane glycoprotein that mediates both receptor recognition and low pH-induced membrane fusion. We have previously demonstrated that a soluble form of the ectodomain of G (G1–439), although secreted, is folded in an alternative conformation, which is monomeric and antigenically distinct from the native state of the complete, membrane-anchored glycoprotein. This has raised questions concerning the role of the transmembrane domain (TMD) in the correct native folding of the ectodomain. Here, we show that an ectodomain anchored in the membrane by a glycophosphatidylinositol is also folded in an alternative conformation, whereas replacement of the TMD of G by other peptide TMDs results in correct antigenicity of G. However, mutants with an insertion of a hydrophilic linker between the ectodomain and the TMD also fold in an alternative conformation. The influence of the membrane-anchor type on G ectodomain trimerization and folding is discussed.
- Published
- 2002
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