The role of single N-glycans in proteolytic processing and cell surface transport of the Lassa virus glycoprotein GP-C

Virol J. 2006 May 31:3:41. doi: 10.1186/1743-422X-3-41.

Abstract

Lassa virus glycoprotein is synthesised as a precursor (preGP-C) into the lumen of the endoplasmic reticulum. After cotranslational cleavage of the signal peptide, the immature GP-C is posttranslationally processed into the N-terminal subunit GP-1 and the C-terminal subunit GP-2 by the host cell subtilase SKI-1/S1P. The glycoprotein precursor contains eleven potential N-glycosylation sites. In this report, we investigated the effect of each N-glycan on proteolytic cleavage and cell surface transport by disrupting the consensus sequences of eleven potential N-glycan attachment sites individually. Five glycoprotein mutants with disrupted N-glycosylation sites were still proteolytically processed, whereas the remaining N-glycosylation sites are necessary for GP-C cleavage. Despite the lack of proteolytic processing, all cleavage-defective mutants were transported to the cell surface and remained completely endo H-sensitive. The findings indicate that N-glycans are needed for correct conformation of GP-C in order to be cleaved by SKI-1/S1P.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Membrane / metabolism
  • Chlorocebus aethiops
  • Glycoproteins / genetics
  • Glycoproteins / metabolism
  • Glycosylation
  • Lassa virus / genetics
  • Lassa virus / metabolism*
  • Mutation
  • Polysaccharides / metabolism*
  • Proprotein Convertases / metabolism
  • Protein Conformation
  • Protein Folding
  • Protein Precursors / genetics
  • Protein Precursors / metabolism
  • Serine Endopeptidases / metabolism
  • Transfection
  • Vero Cells
  • Viral Envelope Proteins / chemistry
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / metabolism*

Substances

  • Glycoproteins
  • Polysaccharides
  • Protein Precursors
  • Viral Envelope Proteins
  • glycoprotein gp1, lassa virus
  • glycoprotein gp2, lassa virus
  • Proprotein Convertases
  • Serine Endopeptidases
  • membrane-bound transcription factor peptidase, site 1