Structure of the HIV-1 Nucleocapsid Protein Bound to the SL3 ψ-RNA Recognition Element

• Published in: Science (American Association for the Advancement of Science) 1998-01, Vol.279 (5349), p.384-388
• Main Authors: de Guzman, Roberto N., Wu, Zheng Rong, Stalling, Chelsea C., Pappalardo, Lucia, Borer, Philip N., Summers, Michael F.
• Format: Article
• Language: English
• Subjects: AIDS/HIV; Amino Acid Sequence; Atoms; Base Sequence; Binding Sites; Biochemistry; Biological and medical sciences; Fundamental and applied biological sciences. Psychology; Gene Products, gag - chemistry; Gene Products, gag - metabolism; Genome, Viral; Genomes; HIV; HIV (Viruses); HIV 1; HIV-1 - chemistry; HIV-1 - genetics; Hydrogen Bonding; Hydrogen bonds; Magnetic Resonance Spectroscopy; Microbiology; Models, Molecular; Molecular Sequence Data; Morphology, structure, chemical composition, physicochemical properties; Nucleic Acid Conformation; Nucleocapsid - chemistry; Nucleocapsid - metabolism; Nucleotides; Packaging; Protein Conformation; Protein Folding; Protein Structure, Secondary; Protons; Receptors; RNA; RNA, Viral - chemistry; RNA, Viral - genetics; RNA, Viral - metabolism; Virology; Virus receptors; Viruses; Zinc; Zinc - chemistry; Zinc - metabolism; Zinc Fingers
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.279.5349.384

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 ψ RNA packaging signal has been determined by heteronuclear magnetic resonance spectroscopy. Tight binding (dissociation constant, ∼100 nM) is mediated by specific interactions between the amino- and carboxyl-terminal CCHC-type zinc knuckles of the NC protein and the G$^7$ and G$^9$ nucleotide bases, respectively, of the G$^6$-G$^7$-A$^8$-G$^9$ RNA tetraloop. A$^8$ packs against the amino-terminal knuckle and forms a hydrogen bond with conserved Arg$^{32}$, and residues Lys$^3$ to Arg$^{10}$ of NC form a 3$_{10}$ 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.