The role of proteolytic processing and the stable signal peptide in expression of the Old World arenavirus envelope glycoprotein ectodomain

Journal Article · Tue Feb 05 04:00:00 EST 2013 · Virology

DOI:https://doi.org/10.1016/J.VIROL.2012.10.038· OSTI ID:22150099

Burri, Dominique J.; Pasquato, Antonella; Ramos da Palma, Joel ^[1]; Igonet, Sebastien; Oldstone, Michael B.A. ^[2]; Kunz, Stefan ^[1]

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1. Institute of Microbiology, University Hospital Center and University of Lausanne, Lausanne CH-1011 (Switzerland)
2. Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037 (United States)

Maturation of the arenavirus GP precursor (GPC) involves proteolytic processing by cellular signal peptidase and the proprotein convertase subtilisin kexin isozyme 1 (SKI-1)/site 1 protease (S1P), yielding a tripartite complex comprised of a stable signal peptide (SSP), the receptor-binding GP1, and the fusion-active transmembrane GP2. Here we investigated the roles of SKI-1/S1P processing and SSP in the biosynthesis of the recombinant GP ectodomains of lymphocytic choriomeningitis virus (LCMV) and Lassa virus (LASV). When expressed in mammalian cells, the LCMV and LASV GP ectodomains underwent processing by SKI-1/S1P, followed by dissociation of GP1 from GP2. The GP2 ectodomain spontaneously formed trimers as revealed by chemical cross-linking. The endogenous SSP, known to be crucial for maturation and transport of full-length arenavirus GPC was dispensable for processing and secretion of the soluble GP ectodomain, suggesting a specific role of SSP in the stable prefusion conformation and transport of full-length GPC.

• OSTI ID: 22150099
• Journal Information: Virology, Journal Name: Virology Journal Issue: 1 Vol. 436; ISSN VIRLAX; ISSN 0042-6822
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
BIOSYNTHESIS
CROSS-LINKING
GLYCOPROTEINS
PEPTIDES
RECEPTORS
VIRUSES