Characterization of the signal peptide processing and membrane association of human cytomegalovirus glycoprotein O.
Human cytomegalovirus (HCMV) has a structurally complex envelope that contains multiple glycoproteins. These glycoproteins are involved in virus entry, virus maturation, and cell-cell spread of infection. Glycoprotein H (gH), glycoprotein L (gL), and glycoprotein O (gO) associate covalently to form a unique disulfide-bonded tripartite complex. Glycoprotein O was recently discovered, and its basic structure, as well as that of the tripartite complex, remains uncharacterized. Based on hydropathy analysis, we hypothesized that gO could adopt a type II transmembrane orientation. The data presented here, however, reveal that the single hydrophobic domain of gO functions as a cleavable signal peptide that is absent from the mature molecule. Although it lacks a membrane anchor, glycoprotein O is associated with the membranes of HCMV-infected cells. The sophisticated organization of the gH.gL.gO complex reflects the intricate nature of the multicomponent entry and fusion machinery encoded by HCMV.
Theiler
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McArdle Laboratory for Cancer Research, University of Wisconsin-Madison Medical School, Madison, Wisconsin 53706, USA.
Compton
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D000595:Amino Acid Sequence; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D003587:Cytomegalovirus / Q000737:chemistry*; D004220:Disulfides; D004591:Electrophoresis, Polyacrylamide Gel; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000378:metabolism; D008954:Models, Biological; D008969:Molecular Sequence Data; D011485:Protein Binding; D014176:Protein Biosynthesis; D021382:Protein Sorting Signals; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D013347:Subcellular Fractions; D014162:Transfection; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000378:metabolism
D004220:Disulfides; D008562:Membrane Glycoproteins; D021382:Protein Sorting Signals; D014759:Viral Envelope Proteins; C439068:glycoprotein O, cytomegalovirus