| dc.creator | York, Joanne | |
| dc.creator | Agnihothram, Sudhakar S. | |
| dc.creator | Romanowski, Víctor | |
| dc.creator | Nunberg, Jack H. | |
| dc.date | 2005 | |
| dc.date | 2019-10-11T12:10:09Z | |
| dc.identifier | http://sedici.unlp.edu.ar/handle/10915/83114 | |
| dc.identifier | issn:0042-6822 | |
| dc.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. | |
| dc.description | Instituto de Biotecnologia y Biologia Molecular | |
| dc.format | application/pdf | |
| dc.format | 267-274 | |
| dc.language | en | |
| dc.rights | http://creativecommons.org/licenses/by-nc-sa/4.0/ | |
| dc.rights | Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) | |
| dc.subject | Bioquímica | |
| dc.subject | Arenavirus | |
| dc.subject | Envelope glycoprotein | |
| dc.subject | GP-C | |
| dc.subject | Junín virus or Argentine hemorrhagic fever virus | |
| dc.subject | Membrane fusion | |
| dc.subject | Mutagenesis | |
| dc.subject | Six-helix bundle | |
| dc.title | Genetic analysis of heptad-repeat regions in the G2 fusion subunit of the Junín arenavirus envelope glycoprotein | |
| dc.type | Articulo | |
| dc.type | Articulo | |
