Removal of zinc is required for processing of the mature nucleocapsid protein of human immunodeficiency virus, type 1, by the viral protease.
In human immunodeficiency virus, RNA selection and packaging during assembly involve the two retroviral-type fingers of the nucleocapsid protein that are held in a constrained configuration by coordinated zinc ions. In this report, we demonstrate that the nucleocapsid protein in a metal bound state is resistant to cleavage by the viral protease, but upon removal of zinc ions by chelating agents, it is hydrolyzed within the first zinc finger between Phe-16 and Asn-17. However, 3-nitrosobenzamide and cupric ions, which release zinc through oxidation of the cysteine residues of the finger, render the nucleocapsid protein resistant to cleavage. Since protease inhibitors and 3-nitrosobenzamide restrict processes relating to steps early in infection, the cleavage of the nucleocapsid protein may represent an essential event that can be exploited for the design of novel antiviral agents.
Wondrak
E M
EM
Laboratory of Cellular and Developmental Biology, NIDDK, National Institutes of Health, Bethesda, Maryland 20892.
Sakaguchi
K
K
Rice
W G
WG
Kun
E
E
Kimmel
A R
AR
Louis
J M
JM
D000595:Amino Acid Sequence; D001549:Benzamides / Q000494:pharmacology; D002213:Capsid / Q000378:metabolism*; D036022:Capsid Proteins; D015683:Gene Products, gag / Q000378:metabolism*; D016333:HIV Protease / Q000378:metabolism*; D015497:HIV-1 / Q000201:enzymology / Q000378:metabolism*; D008969:Molecular Sequence Data; D009603:Nitroso Compounds / Q000494:pharmacology; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D014764:Viral Proteins; D015032:Zinc / Q000378:metabolism*; D016335:Zinc Fingers; D054301:gag Gene Products, Human Immunodeficiency Virus
D001549:Benzamides; D036022:Capsid Proteins; D015683:Gene Products, gag; C071884:NCP7 protein, Human immunodeficiency virus 1; D009603:Nitroso Compounds; D014764:Viral Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus; C076039:3-nitrosobenzamide; D016333:HIV Protease; D015032:Zinc