The nucleocapsid protein isolated from HIV-1 particles binds zinc and forms retroviral-type zinc fingers.
The role of zinc in retroviral gag protein function has been addressed through the application of high-resolution nuclear magnetic resonance spectroscopy to samples of the nucleocapsid protein (NCP, p7) isolated directly from infectious HIV-1 particles. Unlike reports for the NCP from avian myeloblastosis virus (AMV) particles [Jentoft et al. (1988) Proc. Natl. Acad. Sci. U.S.A. 85, 7094], we find that the HIV-1 NCP binds 2 equiv of zinc tightly and stoichiometrically. Two-dimensional NMR spectroscopic studies reveal that zinc binding induces formation of folded domains that are conformationally similar to (if not identical with) structures observed previously for relevant retroviral-type (RT) zinc finger peptides [formerly called zinc fingerlike peptides; Summers et al. (1990) Biochemistry 29, 329]. This finding is consistent with the hypothesis that the inability of mutant proteins (with substituted Cys and His residues) to package viral RNA results from deficient zinc-binding capability, which may have significant consequences in the development of vaccines for the prevention of AIDS.
South
T L
TL
Department of Chemistry and Biochemistry, University of Maryland Baltimore County 21228.
Blake
P R
PR
Sowder
R C
RC
Arthur
L O
LO
Henderson
L E
LE
Summers
M F
MF
D000595:Amino Acid Sequence; D002213:Capsid / Q000302:isolation & purification*; D015497:HIV-1 / Q000032:analysis*; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D014758:Viral Core Proteins / Q000302:isolation & purification*; D014771:Virion / Q000032:analysis*; D015032:Zinc / Q000378:metabolism*; D016335:Zinc Fingers
D014758:Viral Core Proteins; D015032:Zinc