Structure of the HIV-1 nucleocapsid protein bound to the SL3 ψ-RNA recognition element

Roberto N. De Guzman, Zheng Rong Wu, Chelsea C. Stalling, Lucia Pappalardo, Philip N. Borer, Michael F. Summers

Research output: Contribution to journalArticle

569 Scopus citations

Abstract

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 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.

Original languageEnglish (US)
Pages (from-to)384-388
Number of pages5
JournalScience
Volume279
Issue number5349
DOIs
StatePublished - Jan 16 1998

ASJC Scopus subject areas

  • General

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    De Guzman, R. N., Wu, Z. R., Stalling, C. C., Pappalardo, L., Borer, P. N., & Summers, M. F. (1998). Structure of the HIV-1 nucleocapsid protein bound to the SL3 ψ-RNA recognition element. Science, 279(5349), 384-388. https://doi.org/10.1126/science.279.5349.384