Competitive inhibition of human immunodeficiency virus type-1 protease by the Gag-Pol transframe protein.
The human immunodeficiency virus type-1 (HIV-1) transframe protein p6* is located between the structural and enzymatic domains of the Gag-Pol polyprotein, flanked by the nucleocapsid (NC) and the protease (PR) domain at its amino and carboxyl termini, respectively. Here, we report that recombinant highly purified HIV-1 p6* specifically inhibits mature HIV-1 PR activity. Kinetic analyses and cross-linking experiments revealed a competitive mechanism for PR inhibition by p6*. We further demonstrate that the four carboxyl-terminal residues of p6* are essential but not sufficient for p6*-mediated inhibition of PR activity. Based on these results, we suggest a role of the transframe protein p6* in regulating HIV-1 PR activity during viral replication.
Institut für Medizinische Mikrobiologie und Hygiene, Universität Regensburg, Franz-Josef-Strauss-Allee 11, D-93053 Regensburg, Germany.
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C
Paulus
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S
Hellebrand
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Tessmer
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H
Wolf
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HG
Kräusslich
R
R
Wagner
D000595:Amino Acid Sequence; D001667:Binding, Competitive; D003432:Cross-Linking Reagents; D015685:Fusion Proteins, gag-pol / Q000378:metabolism*; D015683:Gene Products, gag / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D016333:HIV Protease / Q000378:metabolism*; D017320:HIV Protease Inhibitors / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008956:Models, Chemical; D016297:Mutagenesis, Site-Directed; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D054301:gag Gene Products, Human Immunodeficiency Virus
D003432:Cross-Linking Reagents; D015685:Fusion Proteins, gag-pol; D015683:Gene Products, gag; D017320:HIV Protease Inhibitors; D011994:Recombinant Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus; C083002:p6 gag protein, Human immunodeficiency virus 1; D016333:HIV Protease