A New Type of Signal Peptidase Cleavage Site Identified in an RNA Virus Polyprotein |
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Authors: | Ioana Bintintan and Gregor Meyers |
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Affiliation: | From the Institut für Immunologie, Friedrich-Loeffler-Institut, Paul-Ehrlich-Strasse 28, D-72001 Tübingen, Germany |
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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 Erns is different because it does not contain a hydrophobic transmembrane region but an amphipathic helix functioning as the Erns membrane anchor. Despite the absence of a hydrophobic region, the site between the C terminus of Erns and E1, the protein located downstream in the polyprotein, is cleaved by signal peptidase, as demonstrated by mutagenesis and inhibitor studies. Thus, ErnsE1 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 Erns 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. |
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Keywords: | Membrane/Proteins Protein/Viral Protein/Processing Viruses/Flavi Enzyme Mechanisms Protein Conformation Protein Folding Amphipathic Helix Signal Peptidase |
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