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• W2163798839 abstract "The arenavirus envelope glycoprotein (GP-C) retains a cleaved and stable signal peptide (SSP) as an essential subunit of the mature complex. This 58-amino-acid residue peptide serves as a signal sequence and is additionally required to enable transit of the assembled GP-C complex to the Golgi, and for pH-dependent membrane fusion activity. We have investigated the C-terminal region of the Junín virus SSP to study the role of the cellular signal peptidase (SPase) in generating SSP. Site-directed mutagenesis at the cleavage site (positions -1 and -3) reveals a pattern of side-chain preferences consistent with those of SPase. Although position -2 is degenerate for SPase cleavage, this residue in the arenavirus SSP is invariably a cysteine. In the Junín virus, this cysteine is not involved in disulfide bonding. We show that replacement with alanine or serine is tolerated for SPase cleavage but prevents the mutant SSP from associating with GP-C and enabling transport to the cell surface. Conversely, an arginine mutation at position -1 that prevents SPase cleavage is fully compatible with GP-C-mediated membrane fusion activity when the mutant SSP is provided in trans. These results point to distinct roles of SSP sequences in SPase cleavage and GP-C biogenesis. Further studies of the unique structural organization of the GP-C complex will be important in identifying novel opportunities for antiviral intervention against arenaviral hemorrhagic disease." @default.
• W2163798839 created "2016-06-24" @default.
• W2163798839 creator A5068845739 @default.
• W2163798839 creator A5072936149 @default.
• W2163798839 date "2007-03-01" @default.
• W2163798839 modified "2023-10-03" @default.
• W2163798839 title "Distinct requirements for signal peptidase processing and function in the stable signal peptide subunit of the Junín virus envelope glycoprotein" @default.
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• W2163798839 doi "https://doi.org/10.1016/j.virol.2006.08.048" @default.
• W2163798839 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/17045626" @default.
• W2163798839 hasPublicationYear "2007" @default.
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