The human immunodeficiency virus type 1 envelope glycoprotein precursor acquires aberrant intermolecular disulfide bonds that may prevent normal proteolytic processing.
The envelope glycoprotein of human immunodeficiency virus consists of two subunits, designated gp120 and gp41, derived from the cleavage of a precursor polypeptide gp160. When expressed from a recombinant vaccinia virus and analyzed by velocity gradient sedimentation and polyacrylamide gel electrophoresis, a significant proportion of gp160 molecules formed oligomers that were stabilized by intermolecular disulfide bonds. Oligomeric forms of both gp120 and gp41 were also observed, but these oligomers were noncovalently associated. Both the intermolecularly linked oligomers of gp160 and the unlinked oligomeric envelope protein subunits were found to accumulate with time. These results indicate that there are two populations of gp160 precursors, one that is folded and processed correctly into gp120 and gp41 and another that is intermolecularly disulfide bonded and remains uncleaved. We propose that the formation of intermolecular disulfide bonds is not an intermediate step in the maturation of the envelope glycoprotein, but rather a result of misfolding of the gp160 precursor which prevents it from being properly processed.
Owens
R J
RJ
Department of Microbiology, University of Alabama, Birmingham 35294.
Compans
R W
RW
D000818:Animals; D001692:Biological Transport; D002451:Cell Compartmentation; D002460:Cell Line; D002499:Centrifugation, Density Gradient; D006224:Cricetinae; D003432:Cross-Linking Reagents; D004220:Disulfides; D015686:Gene Products, env / Q000378:metabolism*; D015699:HIV Envelope Protein gp120 / Q000096:biosynthesis*; D015700:HIV Envelope Protein gp41 / Q000096:biosynthesis*; D015497:HIV-1 / Q000378:metabolism*; D046911:Macromolecular Substances; D008970:Molecular Weight; D011485:Protein Binding; D011498:Protein Precursors / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D011994:Recombinant Proteins
D003432:Cross-Linking Reagents; D004220:Disulfides; D015686:Gene Products, env; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D046911:Macromolecular Substances; D011498:Protein Precursors; D011994:Recombinant Proteins