Rabies virus glycoprotein can fold in two alternative, antigenically distinct conformations depending on membrane-anchor type.
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 (G(1-439)), 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.
Maillard
Antoine P
AP
Laboratoire de Génétique des Virus du CNRS, 91198 Gif sur Yvette Cedex, France1.
Gaudin
Yves
Y
Laboratoire de Génétique des Virus du CNRS, 91198 Gif sur Yvette Cedex, France1.
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D000956:Antigens, Viral / Q000032:analysis / Q000737:chemistry* / Q000276:immunology*; D002460:Cell Line; D004591:Electrophoresis, Polyacrylamide Gel; D004721:Endoplasmic Reticulum / Q000378:metabolism; D000939:Epitopes / Q000276:immunology; D005455:Fluorescent Antibody Technique; D006023:Glycoproteins / Q000032:analysis / Q000737:chemistry* / Q000276:immunology*; D008969:Molecular Sequence Data; D009154:Mutation; D011487:Protein Conformation; D017510:Protein Folding; D011820:Rabies virus / Q000737:chemistry* / Q000276:immunology*; D011995:Recombination, Genetic; D016415:Sequence Alignment; D014759:Viral Envelope Proteins / Q000032:analysis / Q000737:chemistry* / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000956:Antigens, Viral; D000939:Epitopes; D006023:Glycoproteins; D014759:Viral Envelope Proteins; C064951:glycoprotein G, Rabies virus