Synthesis and processing of the major envelope glycoprotein of murine cytomegalovirus.
We have characterized the synthesis and processing pathway of the major envelope glycoprotein complex of murine cytomegalovirus (gp52/105/150). We have demonstrated that it belongs to the "late" kinetic class of MCMV proteins, and is initially synthesized as a 128K glycoprotein (gp128) which contains N-linked, high-mannose type oligosaccharide chains and is phosphorylated predominantly at serine residues. A fraction of the gp128 molecules also contains O-linked GalNAc residues. The majority of the gp128 molecules appears to be retained in the endoplasmic reticulum as evidenced by their sensitivity to endoglycosidase H digestion. The formation of disulfide linkages and dimerization allow the transport of gp128 to the Golgi compartments where modification of N-linked carbohydrate structures and extension of O-linked oligosaccharide chains take place, cumulating in the appearance of the mature gp150. The final processing step involves the cleavage of gp150 into gp52 and gp105. By blocking the transport of the glycoprotein precursor to the trans-Golgi compartments with the ionophore monensin, the cleavage process is inhibited, suggesting that the trans-Golgi compartment is the site where gp150 is cleaved. However, the cleavage process is incomplete, resulting in the formation of multiple disulfide-linked complexes made up of different combinations of gp52, gp105, and gp150. Therefore, the processing of the major envelope glycoprotein complexes of murine cytomegalovirus resembles that of the gcl/gp55-116 complex of human cytomegalovirus.
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LC
Department of Microbiology, University of Saskatchewan, Saskatoon, Canada.
D000818:Animals; D002847:Chromatography, Agarose; D003587:Cytomegalovirus / Q000378:metabolism*; D004220:Disulfides; D004591:Electrophoresis, Polyacrylamide Gel; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008970:Molecular Weight; D008985:Monensin / Q000494:pharmacology; D009844:Oligosaccharides / Q000378:metabolism; D010449:Peptide Mapping; D010766:Phosphorylation; D011233:Precipitin Tests; D011498:Protein Precursors / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D014415:Tunicamycin / Q000494:pharmacology; D014759:Viral Envelope Proteins / Q000096:biosynthesis / Q000378:metabolism*
D004220:Disulfides; D009844:Oligosaccharides; D011498:Protein Precursors; D014759:Viral Envelope Proteins; D014415:Tunicamycin; D008985:Monensin