title: Comparative cellular processing of the human immunodeficiency virus (HIV-1) envelope glycoprotein gp160 by the mammalian subtilisin/kexin-like convertases.
abstract: We present here the pulse and pulse-chase analysis of the biosynthesis of the envelope glycoprotein gp160 and its intracellular processing by the subtilisin/kexin-like convertases furin, PACE4, PC1, PC5 and its isoform PC5/6-B. We demonstrate that furin and to a much lesser extent PACE4, PC5/6-B and PC1 are candidate enzymes capable of processing gp160 intracellularly. Furthermore we show that furin can also process gp160/gp120 into gp77/gp53 products by cleavage at the sequence RIQR/GPGR just preceding the conserved GPGR structure found at the tip of the hypervariable V3 loop. The results show that processing into gp120 could occur at or before the trans-Golgi network (TGN) where sulphation of the oligosaccharide moieties of gp160 was detected. In contrast, the formation of gp77/gp53 by furin is a late event occurring after exit from the TGN. Our data also revealed that the alpha glucosidase I inhibitor N-butyldeoxynojirimycin, although affecting the oligosaccharide composition of gp160, does not impair the processing of either gp160 or gp120 by either furin or PACE4. Finally, the co-expression of the [Arg355, Arg358]-alpha-1-antitrypsin Portland variant was shown to potently inhibit the processing of both gp160 and gp120 by these convertases.
authors.affiliation: J.A. DeSève Laboratories of Biochemical and Molecular Neuroendocrinology, Montréal, Québec, Canada.
authors.forename: F
authors.initials: F
authors.lastname: Vollenweider
authors.forename: S
authors.initials: S
authors.lastname: Benjannet
authors.forename: E
authors.initials: E
authors.lastname: Decroly
authors.forename: D
authors.initials: D
authors.lastname: Savaria
authors.forename: C
authors.initials: C
authors.lastname: Lazure
authors.forename: G
authors.initials: G
authors.lastname: Thomas
authors.forename: M
authors.initials: M
authors.lastname: Chrétien
authors.forename: N G
authors.initials: NG
authors.lastname: Seidah
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002522:Chlorocebus aethiops; D015686:Gene Products, env / Q000378:metabolism*; D006031:Glycosylation; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D019302:HIV Envelope Protein gp160; D006801:Humans; D051379:Mice; D009844:Oligosaccharides / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D013381:Subtilisins / Q000378:metabolism*; D000515:alpha 1-Antitrypsin / Q000494:pharmacology
chemical_list: D015686:Gene Products, env; D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; D009844:Oligosaccharides; D011498:Protein Precursors; D000515:alpha 1-Antitrypsin; D013381:Subtilisins; D002118:Calcium