title: Role of the stable signal peptide of Junín arenavirus envelope glycoprotein in pH-dependent membrane fusion.
abstract: The envelope glycoprotein of the arenaviruses (GP-C) is unusual in that the mature complex retains the cleaved, 58-amino-acid signal peptide. Association of this stable signal peptide (SSP) has been shown to be essential for intracellular trafficking and proteolytic maturation of the GP-C complex. We identify here a specific and previously unrecognized role of SSP in pH-dependent membrane fusion. Amino acid substitutions that alter the positive charge at lysine K33 in SSP affect the ability of GP-C to mediate cell-cell fusion and the threshold pH at which membrane fusion is triggered. Based on the presumed location of K33 at or near the luminal domain of SSP, we postulate that SSP interacts with the membrane-proximal or transmembrane regions of the G2 fusion protein. This unique organization of the GP-C complex may suggest novel strategies for intervention in arenavirus infection.
authors.affiliation: Montana Biotechnology Center, The University of Montana, Science Complex Rm. 221, Missoula, MT 59812, USA.
authors.forename: Joanne
authors.initials: J
authors.lastname: York
authors.forename: Jack H
authors.initials: JH
authors.lastname: Nunberg
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D002459:Cell Fusion; D002522:Chlorocebus aethiops; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D018051:Junin virus / Q000235:genetics / Q000378:metabolism*; D008239:Lysine / Q000235:genetics / Q000378:metabolism; D008561:Membrane Fusion; D008969:Molecular Sequence Data; D011498:Protein Precursors / Q000737:chemistry / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D021382:Protein Sorting Signals / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D006023:Glycoproteins; D011498:Protein Precursors; D021382:Protein Sorting Signals; D014759:Viral Envelope Proteins; D008239:Lysine