title: Differential recognition of Old World and New World arenavirus envelope glycoproteins by subtilisin kexin isozyme 1 (SKI-1)/site 1 protease (S1P).
abstract: The arenaviruses are an important family of emerging viruses that includes several causative agents of severe hemorrhagic fevers in humans that represent serious public health problems. A crucial step of the arenavirus life cycle is maturation of the envelope glycoprotein precursor (GPC) by the cellular subtilisin kexin isozyme 1 (SKI-1)/site 1 protease (S1P). Comparison of the currently known sequences of arenavirus GPCs revealed the presence of a highly conserved aromatic residue at position P7 relative to the SKI-1/S1P cleavage side in Old World and clade C New World arenaviruses but not in New World viruses of clades A and B or cellular substrates of SKI-1/S1P. Using a combination of molecular modeling and structure-function analysis, we found that residue Y285 of SKI-1/S1P, distal from the catalytic triad, is implicated in the molecular recognition of the aromatic "signature residue" at P7 in the GPC of Old World Lassa virus. Using a quantitative biochemical approach, we show that Y285 of SKI-1/S1P is crucial for the efficient processing of peptides derived from Old World and clade C New World arenavirus GPCs but not of those from clade A and B New World arenavirus GPCs. The data suggest that during coevolution with their mammalian hosts, GPCs of Old World and clade C New World viruses expanded the molecular contacts with SKI-1/S1P beyond the classical four-amino-acid recognition sequences and currently occupy an extended binding pocket.
authors.affiliation: Institute of Microbiology, University Hospital Center and University of Lausanne, Lausanne, Switzerland.
authors.forename: Dominique J
authors.initials: DJ
authors.lastname: Burri
authors.forename: Joel Ramos
authors.initials: JR
authors.lastname: da Palma
authors.forename: Nabil G
authors.initials: NG
authors.lastname: Seidah
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Zanotti
authors.forename: Laura
authors.initials: L
authors.lastname: Cendron
authors.forename: Antonella
authors.initials: A
authors.lastname: Pasquato
authors.forename: Stefan
authors.initials: S
authors.lastname: Kunz
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001117:Arenaviridae Infections / Q000201:enzymology* / Q000235:genetics / Q000821:virology; D006477:Arenaviruses, New World / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D018049:Arenaviruses, Old World / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D016466:CHO Cells; D006224:Cricetinae; D006801:Humans; D008969:Molecular Sequence Data; D043484:Proprotein Convertases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D016415:Sequence Alignment; D012697:Serine Endopeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D014759:Viral Envelope Proteins; D043484:Proprotein Convertases; D012697:Serine Endopeptidases; C115575:membrane-bound transcription factor peptidase, site 1
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