Identification of a pH-Sensitive Switch in VSV-G and a Crystal Structure of the G Pre-fusion State Highlight the VSV-G Structural Transition Pathway
| Autor: | Aurélie A. Albertini, Frauke Beilstein, Abbas Abou Hamdan, Hélène Raux, Laura Belot, Malika Ouldali, Yves Gaudin |
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| Přispěvatelé: | Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Rhabdovirus (RHABDO), Département Virologie (Dpt Viro), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
glycoprotein Conformational change Endosome [SDV]Life Sciences [q-bio] Mutant membrane fusion [SDV.BC]Life Sciences [q-bio]/Cellular Biology Endocytosis medicine.disease_cause Transfection General Biochemistry Genetics and Molecular Biology Vesicular stomatitis Indiana virus 03 medical and health sciences 0302 clinical medicine conformational change Viral envelope Viral Envelope Proteins medicine Mutation Molecular Structure Chemistry Lipid bilayer fusion structural basis Cell biology 030104 developmental biology Ectodomain viral entry class III fusion glycoproteins vesicular stomatitis virus rhabdovirus Viral Fusion Proteins 030217 neurology & neurosurgery |
| Zdroj: | Cell Reports Cell Reports, 2020, 32 (7), pp.108042. ⟨10.1016/j.celrep.2020.108042⟩ Cell Reports, Elsevier Inc, 2020, 32 (7), pp.108042. ⟨10.1016/j.celrep.2020.108042⟩ 'Cell Reports ', vol: 32, pages: 108042-1-108042-19 (2020) |
| ISSN: | 2211-1247 |
| Popis: | VSV fusion machinery, like that of many other enveloped viruses, is triggered at low pH in endosomes after virion endocytosis. It was suggested that some histidines could play the role of pH-sensitive switches. By mutating histidine residues H22, H60, H132, H162, H389, H397, H407, and H409, we demonstrate that residues H389 and D280, facing each other in the six-helix bundle of the post-fusion state, and more prominently H407, located at the interface between the C-terminal part of the ectodomain and the fusion domain, are crucial for fusion. Passages of recombinant viruses bearing mutant G resulted in the selection of compensatory mutations. Thus, the H407A mutation in G resulted in two independent compensatory mutants, L396I and S422I. Together with a crystal structure of G, presented here, which extends our knowledge of G pre-fusion structure, this indicates that the conformational transition is initiated by refolding of the C-terminal part of the G ectodomain. |
| Databáze: | OpenAIRE |
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