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Title: Distinct requirements for signal peptidase processing and function in the stable signal peptide subunit of the Junin virus envelope glycoprotein

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 Junin 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 Junin 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-Cmore » 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.« less

Authors:
 [1];  [2]
  1. Montana Biotechnology Center, University of Montana, Science Complex, Room 221, Missoula, MT 59812 (United States)
  2. Montana Biotechnology Center, University of Montana, Science Complex, Room 221, Missoula, MT 59812 (United States). E-mail: jack.nunberg@umontana.edu
Publication Date:
OSTI Identifier:
20976993
Resource Type:
Journal Article
Resource Relation:
Journal Name: Virology; Journal Volume: 359; Journal Issue: 1; Other Information: DOI: 10.1016/j.virol.2006.08.048; PII: S0042-6822(06)00620-9; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ALANINES; ARGININE; CARBON COMPLEXES; CELL MEMBRANES; CLEAVAGE; CYSTEINE; DISULFIDES; GLYCOPROTEINS; MUTAGENESIS; MUTANTS; MUTATIONS; PEPTIDES; PH VALUE; SERINE; VASCULAR DISEASES; VIRUSES

Citation Formats

York, Joanne, and Nunberg, Jack H. Distinct requirements for signal peptidase processing and function in the stable signal peptide subunit of the Junin virus envelope glycoprotein. United States: N. p., 2007. Web. doi:10.1016/j.virol.2006.08.048.
York, Joanne, & Nunberg, Jack H. Distinct requirements for signal peptidase processing and function in the stable signal peptide subunit of the Junin virus envelope glycoprotein. United States. doi:10.1016/j.virol.2006.08.048.
York, Joanne, and Nunberg, Jack H. Thu . "Distinct requirements for signal peptidase processing and function in the stable signal peptide subunit of the Junin virus envelope glycoprotein". United States. doi:10.1016/j.virol.2006.08.048.
@article{osti_20976993,
title = {Distinct requirements for signal peptidase processing and function in the stable signal peptide subunit of the Junin virus envelope glycoprotein},
author = {York, Joanne and Nunberg, Jack H.},
abstractNote = {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 Junin 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 Junin 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.},
doi = {10.1016/j.virol.2006.08.048},
journal = {Virology},
number = 1,
volume = 359,
place = {United States},
year = {Thu Mar 01 00:00:00 EST 2007},
month = {Thu Mar 01 00:00:00 EST 2007}
}
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