The convertases furin and PC1 can both cleave the human immunodeficiency virus (HIV)-1 envelope glycoprotein gp160 into gp120 (HIV-1 SU) and gp41 (HIV-I TM).
Intracellular proteolytic processing of human immunodeficiency virus envelope glycoprotein precursor (gp160) is an essential step for virus infectivity. Northern blot analysis provided evidence that furin and PC1, but not PC2, are expressed in the CD4+ human lymphoblastoid H9 cell line, suggesting the possible participation of these convertases in human immunodeficiency virus (HIV) gp160 proteolytic processing. Purified PC1 and furin cleaved specifically in vitro gp160 into gp120 (HIV-I SU) and gp41 (HIV-I TM). NH2-terminal sequence analysis of the produced gp41 (HIV-I TM) demonstrated that the cleavage occurred within the sequence Arg-Glu-Lys-Arg decreases Ala-Val-Gly-Ile, which is identical to the bond cleaved in vivo. Transition state analog peptides were designed and tested in vitro for their ability to inhibit the PC1- or furin-mediated gp160 cleavage. The best inhibitor was decanoyl-Arg-Lys-Arg-Arg-psi [CH2NH]-Phe-Leu-Gly-Phe-NH2.
Decroly
E
E
Laboratoire de Chimie Physique des Macromolécules aux Interfaces, Université libre de Bruxelles, Belgium.
Vandenbranden
M
M
Ruysschaert
J M
JM
Cogniaux
J
J
Jacob
G S
GS
Howard
S C
SC
Marshall
G
G
Kompelli
A
A
Basak
A
A
Jean
F
F
D000595:Amino Acid Sequence; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D002460:Cell Line; D002522:Chlorocebus aethiops; D045683:Furin; D015686:Gene Products, env / Q000302:isolation & purification / Q000378:metabolism*; D015699:HIV Envelope Protein gp120 / Q000096:biosynthesis*; D019302:HIV Envelope Protein gp160; D015700:HIV Envelope Protein gp41 / Q000096:biosynthesis*; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis / Q000494:pharmacology*; D043484:Proprotein Convertases; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D011498:Protein Precursors / Q000302:isolation & purification / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D013379:Substrate Specificity; D013381:Subtilisins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D015686:Gene Products, env; D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; D015700:HIV Envelope Protein gp41; D009842:Oligopeptides; D011480:Protease Inhibitors; D011498:Protein Precursors; D043484:Proprotein Convertases; D013381:Subtilisins; D045683:Furin; D016282:Aspartic Acid Endopeptidases; D013755:Tetradecanoylphorbol Acetate