Genetic analysis of heptad-repeat regions in the G2 fusion subunit of the Junín arenavirus envelope glycoprotein

The G2 fusion subunit of the Junín virus envelope glycoprotein GP-C contains two hydrophobic heptad-repeat regions that are postulated to form a six-helix bundle structure required for the membrane fusion activity of Class I viral fusion proteins. We have investigated the role of these heptad-repeat...

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Detalles Bibliográficos
Autores principales: York, Joanne, Agnihothram, Sudhakar S., Romanowski, Víctor, Nunberg, Jack H.
Formato: Articulo
Lenguaje:Inglés
Publicado: 2005
Materias:
Bioquímica
Arenavirus
Envelope glycoprotein
GP-C
Junín virus or Argentine hemorrhagic fever virus
Membrane fusion
Mutagenesis
Six-helix bundle
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/83114
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-83114
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Bioquímica
Arenavirus
Envelope glycoprotein
GP-C
Junín virus or Argentine hemorrhagic fever virus
Membrane fusion
Mutagenesis
Six-helix bundle
spellingShingle Bioquímica
Arenavirus
Envelope glycoprotein
GP-C
Junín virus or Argentine hemorrhagic fever virus
Membrane fusion
Mutagenesis
Six-helix bundle
York, Joanne
Agnihothram, Sudhakar S.
Romanowski, Víctor
Nunberg, Jack H.
Genetic analysis of heptad-repeat regions in the G2 fusion subunit of the Junín arenavirus envelope glycoprotein
topic_facet Bioquímica
Arenavirus
Envelope glycoprotein
GP-C
Junín virus or Argentine hemorrhagic fever virus
Membrane fusion
Mutagenesis
Six-helix bundle
description The G2 fusion subunit of the Junín virus envelope glycoprotein GP-C contains two hydrophobic heptad-repeat regions that are postulated to form a six-helix bundle structure required for the membrane fusion activity of Class I viral fusion proteins. We have investigated the role of these heptad-repeat regions and, specifically, the importance of the putative interhelical a and d position sidechains by using alanine-scanning mutagenesis. All the mutant glycoproteins were expressed and transported to the cell surface. Proteolytic maturation at the subtilisin kexin isozyme-1/site-1-protease (SKI-1/S1P) cleavage site was observed in all but two of the mutants. Among the adequately cleaved mutant glycoproteins, four positions in the N-terminal region (I333, L336, L347 and L350) and two positions in the C-terminal region (R392 and W395) were shown to be important determinants of cell-cell fusion. Taken together, our results indicate that α-helical coiled-coil structures are likely critical in promoting arenavirus membrane fusion. These findings support the inclusion of the arenavirus GP-C among the Class I viral fusion proteins and suggest pharmacologic and immunologic strategies for targeting arenavirus infection and hemorrhagic fever.
format Articulo
Articulo
author York, Joanne
Agnihothram, Sudhakar S.
Romanowski, Víctor
Nunberg, Jack H.
author_facet York, Joanne
Agnihothram, Sudhakar S.
Romanowski, Víctor
Nunberg, Jack H.
author_sort York, Joanne
title Genetic analysis of heptad-repeat regions in the G2 fusion subunit of the Junín arenavirus envelope glycoprotein
title_short Genetic analysis of heptad-repeat regions in the G2 fusion subunit of the Junín arenavirus envelope glycoprotein
title_full Genetic analysis of heptad-repeat regions in the G2 fusion subunit of the Junín arenavirus envelope glycoprotein
title_fullStr Genetic analysis of heptad-repeat regions in the G2 fusion subunit of the Junín arenavirus envelope glycoprotein
title_full_unstemmed Genetic analysis of heptad-repeat regions in the G2 fusion subunit of the Junín arenavirus envelope glycoprotein
title_sort genetic analysis of heptad-repeat regions in the g2 fusion subunit of the junín arenavirus envelope glycoprotein
publishDate 2005
url http://sedici.unlp.edu.ar/handle/10915/83114
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AT romanowskivictor geneticanalysisofheptadrepeatregionsintheg2fusionsubunitofthejuninarenavirusenvelopeglycoprotein
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bdutipo_str Repositorios
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