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Science 16 January 1998:
Vol. 279. no. 5349, pp. 384 - 388
DOI: 10.1126/science.279.5349.384
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Reports

Structure of the HIV-1 Nucleocapsid Protein Bound to the SL3 &PSgr;-RNA Recognition Element

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

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, ~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.

R. N. De Guzman, Z. R. Wu, C. C. Stalling, M. F. Summers, Howard Hughes Medical Institute and Department of Chemistry and Biochemistry, University of Maryland-Baltimore County (UMBC), 1000 Hilltop Circle, Baltimore, MD 21250, USA.
L. Pappalardo and P. N. Borer, Department of Chemistry, Syracuse University, Syracuse, NY 13244, USA.
*   To whom correspondence should be addressed.

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Mechanism for nucleic acid chaperone activity of HIV-1 nucleocapsid protein revealed by single molecule stretching.
M. C. Williams, I. Rouzina, J. R. Wenner, R. J. Gorelick, K. Musier-Forsyth, and V. A. Bloomfield (2001)
PNAS
   Abstract »    Full Text »
Identification of Residues of the Moloney Murine Leukemia Virus Nucleocapsid Critical for Viral DNA Synthesis In Vivo.
J. Gonsky, E. Bacharach, and S. P. Goff (2001)
J. Virol. 75, 2616-2626
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Characterization of Rous Sarcoma Virus Gag Particles Assembled In Vitro.
F. Yu, S. M. Joshi, Y. M. Ma, R. L. Kingston, M. N. Simon, and V. M. Vogt (2001)
J. Virol. 75, 2753-2764
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Zinc Finger Structures in the Human Immunodeficiency Virus Type 1 Nucleocapsid Protein Facilitate Efficient Minus- and Plus-Strand Transfer.
J. Guo, T. Wu, J. Anderson, B. F. Kane, D. G. Johnson, R. J. Gorelick, L. E. Henderson, and J. G. Levin (2000)
J. Virol. 74, 8980-8988
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Assembly of Retrovirus Capsid-Nucleocapsid Proteins in the Presence of Membranes or RNA.
G. Zuber, J. McDermott, S. Karanjia, W. Zhao, M. F. Schmid, and E. Barklis (2000)
J. Virol. 74, 7431-7441
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In the beginning: genome recognition, RNA encapsidation and the initiation of complex retrovirus assembly.
N. A. Jewell and L. M. Mansky (2000)
J. Gen. Virol. 81, 1889-1899
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The Double-Stranded RNA-Binding Protein Staufen Is Incorporated in Human Immunodeficiency Virus Type 1: Evidence for a Role in Genomic RNA Encapsidation.
A. J. Mouland, J. Mercier, M. Luo, L. Bernier, L. DesGroseillers, and E. A. Cohen (2000)
J. Virol. 74, 5441-5451
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A 5' Splice Site-Proximal Enhancer Binds SF1 and Activates Exon Bridging of a Microexon.
T. Carlo, R. Sierra, and S. M. Berget (2000)
Mol. Cell. Biol. 20, 3988-3995
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Rescue of Multiple Viral Functions by a Second-Site Suppressor of a Human Immunodeficiency Virus Type 1 Nucleocapsid Mutation.
A. Cimarelli, S. Sandin, S. Höglund, and J. Luban (2000)
J. Virol. 74, 4273-4283
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Basic Residues in Human Immunodeficiency Virus Type 1 Nucleocapsid Promote Virion Assembly via Interaction with RNA.
A. Cimarelli, S. Sandin, S. Höglund, and J. Luban (2000)
J. Virol. 74, 3046-3057
   Abstract »    Full Text »


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