title: A new type of signal peptidase cleavage site identified in an RNA virus polyprotein.
abstract: Pestiviruses, a group of enveloped positive strand RNA viruses belonging to the family Flaviviridae, express their genes via a polyprotein that is subsequently processed by proteases. The structural protein region contains typical signal peptidase cleavage sites. Only the site at the C terminus of the glycoprotein E(rns) is different because it does not contain a hydrophobic transmembrane region but an amphipathic helix functioning as the E(rns) membrane anchor. Despite the absence of a hydrophobic region, the site between the C terminus of E(rns) and E1, the protein located downstream in the polyprotein, is cleaved by signal peptidase, as demonstrated by mutagenesis and inhibitor studies. Thus, E(rns)E1 is processed at a novel type of signal peptidase cleavage site showing a different membrane topology. Prevention of glycosylation or introduction of mutations into the C-terminal region of E(rns) severely impairs processing, presumably by preventing proper membrane interaction or disturbing a conformation critical for the protein to be accepted as a substrate by signal peptidase.
authors.affiliation: Institut für Immunologie, Friedrich-Loeffler-Institut, Paul-Ehrlich-Strasse 28, D-72001 Tübingen, Germany.
authors.forename: Ioana
authors.initials: I
authors.lastname: Bintintan
authors.forename: Gregor
authors.initials: G
authors.lastname: Meyers
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D006023:Glycoproteins / Q000737:chemistry; D006031:Glycosylation; D008565:Membrane Proteins / Q000737:chemistry*; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009154:Mutation; D010957:Plasmids / Q000378:metabolism; D020815:Polyproteins / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D012328:RNA Viruses / Q000737:chemistry*; D012697:Serine Endopeptidases / Q000737:chemistry*
chemical_list: D006023:Glycoproteins; D008565:Membrane Proteins; D020815:Polyproteins; D012697:Serine Endopeptidases; C026515:type I signal peptidase