Structure of the HIV-1 nucleocapsid protein bound to the SL3 psi-RNA recognition element.
The three-dimensional structure of the human immunodeficiency virus-type 1 (HIV-1) nucleocapsid protein (NC) bound to the SL3 stem-loop recognition element of the genomic Psi RNA packaging signal has been determined by heteronuclear magnetic resonance spectroscopy. Tight binding (dissociation constant, approximately 100 nM) is mediated by specific interactions between the amino- and carboxyl-terminal CCHC-type zinc knuckles of the NC protein and the G7 and G9 nucleotide bases, respectively, of the G6-G7-A8-G9 RNA tetraloop. A8 packs against the amino-terminal knuckle and forms a hydrogen bond with conserved Arg32, and residues Lys3 to Arg10 of NC form a 310 helix that binds to the major groove of the RNA stem and also packs against the amino-terminal zinc knuckle. The structure provides insights into the mechanism of viral genome recognition, explains extensive amino acid conservation within NC, and serves as a basis for the development of inhibitors designed to interfere with genome encapsidation.
De Guzman
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RN
Howard Hughes Medical Institute and Department of Chemistry and Biochemistry, University of Maryland-Baltimore County (UMBC), 1000 Hilltop Circle, Baltimore, MD 21250, USA.
Wu
Z R
ZR
Stalling
C C
CC
Pappalardo
L
L
Borer
P N
PN
Summers
M F
MF
D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D015683:Gene Products, gag / Q000737:chemistry* / Q000378:metabolism; D016679:Genome, Viral; D015497:HIV-1 / Q000737:chemistry* / Q000235:genetics; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D019251:Nucleocapsid / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D012367:RNA, Viral / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D015032:Zinc / Q000737:chemistry / Q000378:metabolism; D016335:Zinc Fingers
D015683:Gene Products, gag; D012367:RNA, Viral; D015032:Zinc