Formation and rearrangement of disulfide bonds during maturation of the Sindbis virus E1 glycoprotein.
The rigidly ordered icosahedral lattice of the Sindbis virus envelope is composed of a host-derived membrane bilayer in which the viral glycoproteins E1 and E2 reside. E1-E1 interactions stabilized by intramolecular disulfide bridges play a significant role in maintaining the envelope's structural integrity (R. P. Anthony and D. T. Brown, J. Virol. 65:1187-1194, 1991; R. P. Anthony, A. M. Paredes, and D. T. Brown, Virology 190:330-336, 1992). We have examined the acquisition of disulfide bridges within E1 during its maturation. Prior to exit from the endoplasmic reticulum, E1 folds via at least three intermediates, differing in the number and/or arrangement of their disulfides, into a single, compact form. This E1 species remains stable with respect to its disulfides until late in the secretory pathway, when E1 attains a metastable conformation. At this point, when appropriately triggered, intramolecular thiol-disulfide exchange reactions within E1 can occur, resulting in the generation of alternative E1 species. This metastable nature of mature E1 may have important implications for the mechanism of virus disassembly during the initial stages of the infection process (B. Abell and D. T. Brown, J. Virol. 67:5496-5501, 1993).
Mulvey
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Cell Research Institute, University of Texas at Austin 78713-7640.
Brown
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D000818:Animals; D001692:Biological Transport; D002451:Cell Compartmentation; D002478:Cells, Cultured; D006224:Cricetinae; D004220:Disulfides / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism*; D011487:Protein Conformation; D017510:Protein Folding; D011498:Protein Precursors / Q000378:metabolism; D012845:Sindbis Virus / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000378:metabolism*; D014771:Virion / Q000737:chemistry
D004220:Disulfides; D008562:Membrane Glycoproteins; D011498:Protein Precursors; D014759:Viral Envelope Proteins; C022012:glycoprotein E1, Sindbis virus