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Characterization and molecular basis of the oligomeric structure of HIV-1 Nef protein

  1. Stefan Arold1,†,
  2. François Hoh1,
  3. Stephanie Domergue1,
  4. Catherine Birck2,
  5. Marc-André Delsuc1,
  6. Magali Jullien1,
  7. Christian Dumas1,*

Article first published online: 31 DEC 2008

DOI: 10.1110/ps.9.6.1137

Issue

Protein Science

Protein Science

Volume 9, Issue 6, pages 1137–1148, 2000

Additional Information

How to Cite

Arold, S., Hoh, F., Domergue, S., Birck, C., Delsuc, M.-A., Jullien, M. and Dumas, C. (2000), Characterization and molecular basis of the oligomeric structure of HIV-1 Nef protein. Protein Science, 9: 1137–1148. doi: 10.1110/ps.9.6.1137

Author Information

  1. 1

    Centre de Biochimie Structurale, UMR C5048 CNRS, U414 INSERM, Université Montpellier I, Avenue C. Flahault, 34060 Montpellier, France

  2. 2

    Groupe de Cristallographie Biologique, IPBS-CNRS, 31077 Toulouse, France

  1. †

    Laboratory of Molecular Biophysics, South Parks Road, Oxford, United Kingdom

*Centre de Biochimie Structurale, 15 avenue C. Flahault, F34060 Montpellier, France

Publication History

  1. Issue published online: 31 DEC 2008
  2. Article first published online: 31 DEC 2008
  3. Manuscript Accepted: 21 APR 2000
  4. Manuscript Revised: 6 MAR 2000
  5. Manuscript Received: 3 NOV 1999

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  • Ministére de l Enseignement Supérieur de la Recherche

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References

  • Aiken C, Konner J, Landau NR, Lenburg ME, Trono D. 1994. Nef induces CD4 endocytosis: Requirement for a critical dileucine motif in the membrane-proximal CD4 cytoplasmic domain. Cell 76: 853–864.
  • Arold S, Franken P, Strub MP, Hoh F, Benichou S, Benarous R, Dumas C. 1997. The crystal structure of HIV-1 Nef protein bound to the Fyn kinase SH3 domain suggests a role for this complex in altered T cell receptor signaling. Structure 5: 1361–1372.
  • Arold S, O'Brien R, Franken P, Hoh F, Strub M-P, Dumas C, Ladbury J. 1998. RT loop flexibility enhances the specificity of Src family SH3 domains for HIV-1 Nef. Biochemistry 37: 14683–14691.
  • Barnham KJ, Monks SA, Hinds MG, Azad AA, Norton RS. 1997. Solution structure of a polypeptide from the N terminus of the HIV protein Nef. Biochemistry 36: 5970–5980.
  • Baur AS, Sawai ET, Dazin P, Fantl WJ, Cheng-Mayer C, Peterlin BM. 1994. HIV-1 Nef leads to inhibition or activation of T cells depending on its intracellular localization. Immunity 1: 373–384.
  • Benichou S, Bomsel M, Bodeus M, Durand H, Doute M, Letourneur F, Camonis J, Benarous R. 1994. Physical interaction of the HIV-1 Nef protein with beta-COP, a component of non-clathrin-coated vesicles essential for membrane traffic. J Biol Chem 269: 30073–30076.
  • Boyer M, Roy MO, Jullien M. 1996. Dynamic light scattering study of precrystallizing ribonuclease solutions. J Crystal Growth 167: 212–220.
  • Bresnahan PA, Yonemoto W, Ferrell S, Williams-Herman D, Geleziunas R, Greene WC. 1998. A dileucine motif in HIV-1 Nef acts as an internalization signal for CD4 downregulation and binds the AP-1 clathrin adaptor. Curr Biol 8: 1235–1238.
  • Capps GG, Robinson BE, Lewis KD, Zuniga MC. 1993. In vivo dimeric association of class I MHC heavy chains. Possible relationship to class I MHC heavy chain-beta 2-microglobulin dissociation. J Immunol 151: 159–169.
  • Carugo O, Argos P. 1997. Protein-protein crystal-packing contacts. Protein Sci 6: 2261–2263.
    Direct Link:
  • CCP4 (Collaborative Computational Project Number 4). 1994. The CCP4 suite: Programs for protein crystallography. Acta Crystallogr D50: 760–763.
  • Chen YL, Trono D, Camaur D. 1998. The proteolytic cleavage of human immunodeficiency virus type 1 Nef does not correlate with its ability to stimulate virion infectivity. J Virol 72: 3178–3184.
  • Chothia C, Janin J. 1975. Principles of protein-protein recognition. Nature 256: 705–708.
  • Chowers MY, Spina CA, Kwoh TJ, Fitch NJ, Richman DD, Guatelli JC. 1994. Optimal infectivity in vitro of human immunodeficiency virus type 1 requires an intact nef gene. J Virol 68: 2906–2914.
  • Collette Y, Dutartre H, Benziane A, Ramos MF, Benarous R, Harris M, Olive D. 1996. Physical and functional interaction of Nef with Lck. HIV-1 Nefinduced T-cell signaling defects. J Biol Chem 271: 6333–6341.
  • Conte LL, Chothia C, Janin J. 1999. The atomic structure of protein-protein recognition sites. J Mol Biol 285: 2177–2198.
  • Craig HM, Pandori MW, Guatelli JC. 1998. Interaction of HIV-1 Nef with the cellular dileucine-based sorting pathway is required for CD4 down-regulation and optimal viral infectivity. Proc Natl Acad Sci USA 95: 11229–11234.
  • Cullen BR. 1998. HIV-1 auxiliary proteins: Making connections in a dying cell. Cell 93: 685–692.
  • Deacon NJ, Tsykin A, Solomon A, Smith K, Ludford-Menting M, Hooker DJ, McPhee DA, Greenway AL, Ellett A, Chatfield C, et al. 1995. Genomic structure of an attenuated quasi species of HIV-1 from a blood transfusion donor and recipients. Science 270: 988–991.
  • Delsuc MA, Malliavin TE. 1998. Maximum entropy processing of DOSY NMR spectra. Anal Chem 70: 2146–2148.
  • Du Z, Lang SM, Sasseville VG, Lackner AA, Ilyinskii PO, Daniel MD, Jung JU, Desrosiers RC. 1995. Identification of a nef allele that causes lymphocyte activation and acute disease in macaque monkeys. Cell 82: 665–674.
  • Franken P, Arold S, Padilla A, Bodeus M, Hoh F, Strub MP, Boyer M, Jullien M, Benarous R, Dumas C. 1997. HIV-1 Nef protein: Purification, crystallizations, and preliminary X-ray diffraction studies. Protein Sci 6: 2681–2683.
    Direct Link:
  • Freund J, Kellner R, Houthaeve T, Kalbitzer HR. 1994a. Stability and proteolytic domains of Nef protein from human immunodeficiency virus (HIV) type 1. Eur J Biochem 221: 811–819.
    Direct Link:
  • Freund J, Kellner R, Konvalinka J, Wolber V, Krausslich HG, Kalbitzer HR. 1994b. A possible regulation of negative factor (Nef) activity of human immunodeficiency virus type 1 by the viral protease. Eur J Biochem 223: 589–593.
    Direct Link:
  • Fujii Y, Otake K, Fujita Y, Yamamoto N, Nagai Y, Tashiro M, Adachi A. 1996. Clustered localization of oligomeric Nef protein of human immunodeficiency virus type 1 on the cell surface. FEBS Lett 395: 257–261.
  • Gaedigk-Nitschko K, Schon A, Wachinger G, Erfle V, Kohleisen B. 1995. Cleavage of recombinant and cell derived human immunodeficiency virus 1 (HIV-1) Nef protein by HIV-1 protease. FEBS Lett 357: 275–278.
  • Garcia Bernal JM, Garcia de la Torre J. 1981. Transport properties of oligomeric subunit structures. Biopolymers 20: 129–139.
    Direct Link:
  • Garcia JV, Miller AD. 1994. Retrovirus vector-mediated transfer of functional HIV-1 regulatory genes. AIDS Res Hum Retroviruses 10: 47–52.
  • Garcia KC, Teyton L, Wilson IA. 1999. Structural basis of T cell recognition. Annu Rev Immunol 17: 369–397.
  • Geyer M, Munte CE, Schorr J, Kellner R, Kalbitzer HR. 1999. Structure of the anchor-domain of myristoylated and non-myristoylated HIV-1 Nef protein. J Mol Biol 289: 123–138.
  • Greenberg M, DeTulleo L, Rapoport I, Skowronski J, Kirchhausen T. 1998a. A dileucine motif in HIV-1 Nef is essential for sorting into clathrin-coated pits and for downregulation of CD4. Curr Biol 8: 1239–1242.
  • Greenberg ME, Bronson S, Lock M, Neumann M, Pavlakis GN, Skowronski J. 1997. Co-localization of HIV-1 Nef with the AP-2 adaptor protein complex correlates with Nef-induced CD4 down-regulation. EMBO J 16: 6964–6976.
  • Greenberg ME, Iafrate AJ, Skowronski J. 1998b. The SH3 domain-binding surface and an acidic motif in HIV-1 Nef regulate trafficking of class I MHC complexes. EMBO J 17: 2777–2789.
  • Greenway A, Azad A, McPhee D. 1995. Human immunodeficiency virus type 1 Nef protein inhibits activation pathways in peripheral blood mononuclear cells and T-cell lines. J Virol 69: 1842–1850.
  • Grzesiek S, Bax A, Clore GM, Gronenborn AM, Hu JS, Kaufman J, Palmer I, Stahl SJ, Wingfield PT. 1996a. The solution structure of HIV-1 Nef reveals an unexpected fold and permits delineation of the binding surface for the SH3 domain of Hck tyrosine protein kinase. Nat Struct Biol 3: 340–345.
  • Grzesiek S, Bax A, Hu JS, Kaufman J, Palmer I, Stahl SJ, Tjandra N, Wingfield PT. 1997. Refined solution structure and backbone dynamics of HIV-1 Nef. Protein Sci 6: 1248–1263.
    Direct Link:
  • Grzesiek S, Stahl SJ, Wingfield PT, Bax A. 1996b. The CD4 determinant for downregulation by HIV-1 Nef directly binds to Nef. Mapping of the Nef binding surface by NMR. Biochemistry 35: 10256–10261.
  • Hanna Z, Kay DG, Rebai N, Guimond A, Jothy S, Jolicoeur P. 1998. Nef harbors a major determinant of pathogenicity for an AIDS-like disease induced by HIV-1 in transgenic mice. Cell 95: 163–175.
  • Harris MP, Neil JC. 1994. Myristoylation-dependent binding of HIV-1 Nef to CD4. J Mol Biol 241: 136–142.
  • Hensley P. 1996. Defining the structure and stability of macromolecular assemblies in solution: The re-emergence of analytical ultracentrifugation as a practical tool. Structure 4: 367–373.
  • Howe AY, Jung JU, Desrosiers RC. 1998. Zeta chain of the T-cell receptor interacts with nef of simian immunodeficiency virus and human immuno-deficiency virus type 2. J Virol 72: 9827–9834.
  • Iafrate AJ, Bronson S, Skowronski J. 1997. Separable functions of Nef disrupt two aspects of T cell receptor machinery: CD4 expression and CD3 signaling. EMBO J 16: 673–684.
  • Janin J, Chothia C. 1990. The structure of protein-protein recognition sites. J Biol Chem 265: 16027–16030.
  • Janin J, Rodier F. 1995. Protein-protein interaction at crystal contacts. Proteins 23: 580–587.
    Direct Link:
  • Johnson CS, Gabriel DA. 1981. NMR spectroscopy. In: BellEJ, ed. Spectroscopy in biochemistry, Vol. 2. Boca Raton, Florida: CRC Press. p 178.
  • Johnson ML, Correia JJ, Yphantis DA, Halvorson HR. 1981. Analysis of data from the analytical ultracentrifuge by nonlinear least-squares techniques. Biophys J 36: 575–588.
  • Jones S, Thornton JM. 1997. Analysis of protein-protein interaction sites using surface patches. J Mol Biol 272: 121–132.
  • Kienzle N, Freund J, Kalbitzer HR, Mueller-Lantzsch N. 1993. Oligomerization of the Nef protein from human immunodeficiency virus (HIV) type 1. Eur J Biochem 214: 451–457.
    Direct Link:
  • Kirchhoff F, Greenough TC, Brettler DB, Sullivan JL, Desrosiers RC. 1995. Brief report: Absence of intact nef sequences in a long-term survivor with nonprogressive HIV-1 infection. N Engl J Med 332: 228–232.
  • Klemm JD, Schreiber SL, Crabtree GR. 1998. Dimerization as a regulatory mechanism in signal transduction. Annu Rev Immunol 16: 569–592.
  • Koppel DE. 1972. Analysis of macromolecular polydispersity in intensity correlation spectroscopy: The methods of cumulants. J Chem Phys 57: 4814–4820.
  • Krishnan VV, Cosman M. 1998. An empirical relationship between rotational correlation time and solvent accessible surface area. J Biomol NMR 12: 177–182.
  • Laue TM, Shah BD, Ridgeway TM, Pelletier SL. 1992. Computer-aided inter-pretation of omalytical sedimentation data for protins. In: HardingSR, RoweAJ, HortonJC, eds. Analytical ultracentrifugation in biochemistry and polymer science. Cambridge, UK: The Royal Society of Chemistry. pp 90–125.
  • Lee CH, Leung B, Lemmon MA, Zheng J, Cowburn D, Kuriyan J, Saksela K. 1995. A single amino acid in the SH3 domain of Hck determines its high affinity and specificity in binding to HIV-1 Nef protein. EMBO J 14: 5006–5015.
  • Lee CH, Saksela K, Mirza UA, Chait BT, Kuriyan J. 1996. Crystal structure of the conserved core of HIV-1 Nef complexed with a Src family SH3 domain. Cell 85: 931–942.
  • Le Gall S, Erdtmann L, Benichou S, Berlioz-Torrent C, Liu L, Benarous R, Heard JM, Schwartz O. 1998. Nef interacts with the mu subunit of clathrin adaptor complexes and reveals a cryptic sorting signal in MHCI molecules. Immunity 8: 483–495.
  • Liu LX, Heveker N, Fackler OT, Arold S, Le Gall S, Janvier K, Peterlin BM, Dumas C, Schwartz O, Benichou S, Benarous R. 2000. Mutation of a conserved residue (D123) required for oligomerization of human immunodeficiency virus type 1 nef protein abolishes interaction with human thioesterase and results in impairment of nef biological functions. J Virol 74: 5310–5319.
  • Liu LX, Margottin F, Le Gall S, Schwartz O, Selig L, Benarous R, Benichou S. 1997. Binding of HIV-1 Nef to a novel thioesterase enzyme correlates with Nef-mediated CD4 down-regulation. J Biol Chem 272: 13779–13785.
  • Manninen A, Hiipakka M, Vihinen M, Lu W, Mayer BJ, Saksela K. 1998. SH3-Domain binding function of HIV-1 Nef is required for association with a PAK-related kinase. Virology 250: 273–282.
  • Mariani R, Kirchhoff F, Greenough TC, Sullivan JL, Desrosiers RC, Skowronski J. 1996. High frequency of defective nef alleles in a long-term survivor with nonprogressive human immunodeficiency virus type 1 infection. J Virol 70: 7752–7764.
  • Miller MD, Feinberg MB, Greene WC. 1994. The HIV-1 nef gene acts as a positive viral infectivity factor. Trends Microbiol 2: 294–298.
  • Miller MD, Warmerdam MT, Ferrell SS, Benitez R, Greene WC. 1997. Intra-virion generation of the C-terminal core domain of HIV-1 Nef by the HIV-1 protease is insufficient to enhance viral infectivity. Virology 234: 215–225.
  • Morrison ID, Grabowski EF, Herb CA. 1985. Improved techniques for particle size determination by quasi elastic light scattering. Langmuir 1: 496–501.
  • Nicholls A, Sharp KA, Honig B. 1991. Protein folding and association: Insights from the interfacial and thermodynamic properties of hydrocarbons. Proteins 11: 281–296.
    Direct Link:
  • Owen DJ, Evans PR. 1998. A structural explanation for the recognition of tyrosine-based endocytotic signals. Science 282: 1327–1332.
  • Pandori MW, Fitch NJ, Craig HM, Richman DD, Spina CA, Guatelli JC. 1996. Producer-cell modification of human immunodeficiency virus type 1: Nef is a virion protein. J Virol 70: 4283–4290.
  • Piguet V, Chen YL, Mangasarian A, Foti M, Carpentier JL, Trono D. 1998. Mechanism of Nef-induced CD4 endocytosis: Nef connects CD4 with the mu chain of adaptor complexes. EMBO J 17: 2472–2481.
  • Piguet V, Gu F, Foti M, Demaurex N, Gruenberg J, Carpentier JL, Trono D. 1999. Nef-induced CD4 degradation: A diacidic-based motif in Nef functions as a lysosomal targeting signal through the binding of beta-COP in endosomes. Cell 97: 63–73.
  • Pons JL, Malliavin T, Delsuc MA. 1996. Gifa V4: A complete package for NMR data-set processing. J Biomol NMR 8: 445–452.
  • Rossi F, Gallina A, Milanesi G. 1996. Nef-CD4 physical interaction sensed with the yeast two-hybrid system. Virology 217: 397–403.
  • Saksela K. 1997. HIV-1 Nef and host cell protein kinases. Front Biosci 2: 606–618.
  • Saksela K, Cheng G, Baltimore D. 1995. Proline-rich (PxxP) motifs in HIV-1 Nef bind to SH3 domains of a subset of Src kinases and are required for the enhanced growth of Nef+ viruses but not for down-regulation of CD4. EMBO J 14: 484–491.
  • Sawai ET, Khan IH, Montbriand PM, Peterlin BM, Cheng-Mayer C, Luciw PA. 1996. Activation of PAK by HIV and SIV Nef: Importance for AIDS in rhesus macaques. Curr Biol 6: 1519–1527.
  • Schorr J, Kellner R, Fackler O, Freund J, Konvalinka J, Kienzle N, Krausslich HG, Mueller-Lantzsch N, Kalbitzer HR. 1996. Specific cleavage sites of Nef proteins from human immunodeficiency virus types 1 and 2 for the viral proteases. J Virol 70: 9051–9054.
  • Schwartz O, Marechal V, Danos O, Heard JM. 1995. Human immunodeficiency virus type 1 Nef increases the efficiency of reverse transcription in the infected cell. J Virol 69: 4053–4059.
  • Schwartz O, Marechal V, Le Gall S, Lemonnier F, Heard JM. 1996. Endocytosis of major histocompatibility complex class I molecules is induced by the HIV-1 Nef protein. Nat Med 2: 338–342.
  • Welker R, Kottler H, Kalbitzer HR, Krausslich HG. 1996. Human immunodeficiency virus type 1 Nef protein is incorporated into virus particles and specifically cleaved by the viral proteinase. Virology 219: 228–236.
  • Wen J, Arakawa T, Philo JS. 1996. Size-exclusion chromatography with on-line light-scattering, absorbance, and refractive index detectors for studying proteins and their interactions. Anal Biochem 240: 155–166.
  • Wiskerchen M, Cheng-Mayer C. 1996. HIV-1 Nef association with cellular serine kinase correlates with enhanced virion infectivity and efficient proviral DNA synthesis. Virology 224: 292–301.
  • Wray V, Mertins D, Kiess M, Henklein P, Trowitzsch-Kienast W, Schubert U. 1998. Solution structure of the cytoplasmic domain of the human CD4 glycoprotein by CD and 1H NMR spectroscopy: Implications for biological functions. Biochemistry 37: 8527–8538.
  • Wu DH, Chen AD, Johnson CS. 1995. An improved diffusion-ordered spectroscopy experiment incorporating bipolar-gradient pulses. J Magn Reson Ser A 115: 260–264.
  • Wu H, Kwong PD, Hendrickson WA. 1997. Dimeric association and segmental variability in the structure of human CD4. Nature 387: 527–530.
  • Xu XN, Laffert B, Screaton GR, Kraft M, Wolf D, Kolanus W, Mongkolsapay J, McMichael AJ, Baur AS. 1999. Induction of Fas ligand expression by HIV involves the interaction of Nef with the T cell receptor zeta chain. J Exp Med 189: 1489–1496.
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