A new type of signal peptidase cleavage site identified in an RNA virus polyprotein

J Biol Chem. 2010 Mar 19;285(12):8572-84. doi: 10.1074/jbc.M109.083394. Epub 2010 Jan 21.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Cricetinae
  • Glycoproteins / chemistry
  • Glycosylation
  • Membrane Proteins / chemistry*
  • Molecular Sequence Data
  • Mutagenesis
  • Mutation
  • Plasmids / metabolism
  • Polyproteins / chemistry*
  • Protein Structure, Tertiary
  • RNA Viruses / chemistry*
  • Serine Endopeptidases / chemistry*


  • Glycoproteins
  • Membrane Proteins
  • Polyproteins
  • Serine Endopeptidases
  • type I signal peptidase