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Science in China Series C: Life Sciences

, Volume 52, Issue 5, pp 439–449 | Cite as

Structure and sequence analysis of influenza A virus nucleoprotein

  • Andy Ka-Leung Ng
  • Jia-Huai Wang
  • Pang-Chui Shaw
Special Topic Review

Abstract

Influenza A virus nucleoprotein (NP) forms homo-oligomers and multiple copies of NP wrap around genomic RNA, along with a trimeric polymerase making up ribonucleoprotein (RNP) complex. Sequence comparison of more than 2500 influenza A NP showed that this protein contains 30.1 % of polymorphic residues. NP is composed of a head and a body domain and a tail loop/ linker region. The head domain is more conserved than the body domain, as revealed from the structure-based sequence alignment. NP oligomerization is mediated by the insertion of the non-polymorphic and structurally conserved tail loop of one NP molecule to a groove of another NP. The different form of NP oligomers is due to the flexibility of the polymorphic linkers that join the tail loop to the rest of the protein. The RNA binding property of NP is known to involve the protruding element and the flexible basic loop between the head and body domains, both having high degree of primary sequence conservation. To bind RNA, NP may first capture the RNA by the flexible basic loop and then the RNA is clamped by the protruding element.

Keywords

Influenza H5N1 nucleoprotein oligomerization RNA binding 

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References

  1. 1.
    Johnson N P, Mueller J. Updating the accounts: global mortality of the 1918-1920 “Spanish” influenza pandemic. Bull Hist Med, 2002, 76: 105–115, 11875246, 10.1353/bhm.2002.0022CrossRefGoogle Scholar
  2. 2.
    Kilbourne E D. Influenza pandemics of the 20th century. Emerg Infect Dis, 2006, 12: 9–14, 16494710CrossRefGoogle Scholar
  3. 3.
    Yuen K Y, Chan P K, Peiris M, et al. Clinical features and rapid viral diagnosis of human disease associated with avian influenza A H5N1 virus. Lancet, 1998, 351: 467–471, 9482437, 10.1016/S0140-6736(98)01182-9, 1:STN:280:DyaK1c7ktFGnsw%3D%3DCrossRefGoogle Scholar
  4. 4.
    World Health Organization. Confirmed human cases of avian influenza A (H5N1). 2009, available at http://www.who.int/csr/disease/avian_influenza/en
  5. 5.
    Normile D. Avian influenza. WHO proposes plan to stop pandemic in its tracks. Science, 2006, 311: 315–316, 16424302, 10.1126/science.311.5759.315, 1:CAS:528:DC%2BD28Xntl2rsQ%3D%3DCrossRefGoogle Scholar
  6. 6.
    Portela A, Digard P. The influenza virus nucleoprotein: a multifunctional RNA-binding protein pivotal to virus replication. J Gen Virol, 2002, 83: 723–734, 11907320, 1:CAS:528:DC%2BD38XislGhsrY%3DCrossRefGoogle Scholar
  7. 7.
    Noda T, Sagara H, Yen A, et al. Architecture of ribonucleoprotein complexes in influenza A virus particles. Nature, 2006, 439: 490–492, 16437116, 10.1038/nature04378, 1:CAS:528:DC%2BD28XntFWlsQ%3D%3DCrossRefGoogle Scholar
  8. 8.
    Kobayashi M, Toyoda T, Adyshev D M, et al. Molecular dissection of influenza virus nucleoprotein: deletion mapping of the RNA binding domain. J Virol, 1994, 68: 8433–8436, 7966640, 1:CAS:528:DyaK2MXitFyltL8%3DGoogle Scholar
  9. 9.
    Prokudina-Kantorovich E N, Semenova N P. Intracellular oligomerization of influenza virus nucleoprotein. Virology, 1996, 223: 51–56, 8806539, 10.1006/viro.1996.0454, 1:CAS:528:DyaK28XlsVemsbc%3DCrossRefGoogle Scholar
  10. 10.
    Biswas S K, Boutz P L, Nayak D P. Influenza virus nucleoprotein interacts with influenza virus polymerase proteins. J Virol, 1998, 72: 5493–5501, 9621005, 1:CAS:528:DyaK1cXjvFGlsr4%3DGoogle Scholar
  11. 11.
    Skorko R, Summers D F, Galarza J M. Influenza A virus in vitro transcription: roles of NS1 and NP proteins in regulating RNA synthesis. Virology, 1991, 180: 668–677, 1824905, 10.1016/0042-6822(91)90080-U, 1:CAS:528:DyaK3MXnvVCksg%3D%3DCrossRefGoogle Scholar
  12. 12.
    Shapiro G I, Krug R M. Influenza virus RNA replication in vitro: synthesis of viral template RNAs and virion RNAs in the absence of an added primer. J Virol, 1988, 62: 2285–2290, 2453679, 1:CAS:528:DyaL1cXkslSitrc%3DGoogle Scholar
  13. 13.
    Hsu M T, Parvin J D, Gupta S, et al. Genomic RNAs of influenza viruses are held in a circular conformation in virions and in infected cells by a terminal panhandle. Proc Natl Acad Sci USA, 1987, 84: 8140–8144, 2446318, 10.1073/pnas.84.22.8140, 1:CAS:528:DyaL1cXhvV2nsw%3D%3DCrossRefGoogle Scholar
  14. 14.
    Fodor E, Pritlove D C, Brownlee G G. The influenza virus panhandle is involved in the initiation of transcription. J Virol, 1994, 68: 4092–4096, 8189550, 1:CAS:528:DyaK2cXkt1yntro%3DGoogle Scholar
  15. 15.
    Klumpp K, Ruigrok R W, Baudin F. Roles of the influenza virus polymerase and nucleoprotein in forming a functional RNP structure. Embo J, 1997, 16: 1248–1257, 9135141, 10.1093/emboj/16.6.1248, 1:CAS:528:DyaK2sXitlOisbk%3DCrossRefGoogle Scholar
  16. 16.
    Mena I, Jambrina E, Albo C, et al. Mutational analysis of influenza A virus nucleoprotein: identification of mutations that affect RNA replication. J Virol, 1999, 73: 1186–1194, 9882320, 1:CAS:528:DyaK1MXmtlajsw%3D%3DGoogle Scholar
  17. 17.
    Ye Q, Krug R M, Tao Y J. The mechanism by which influenza A virus nucleoprotein forms oligomers and binds RNA. Nature, 2006, 444: 1078–1082, 17151603, 10.1038/nature05379, 1:CAS:528:DC%2BD28XhtlemtLbICrossRefGoogle Scholar
  18. 18.
    Ng A K, Zhang H, Tan K, et al. Structure of the influenza virus A H5N1 nucleoprotein: implications for RNA binding, oligomerization, and vaccine design. Faseb J, 2008, 22: 3638–3647, 18614582, 10.1096/fj.08-112110, 1:CAS:528:DC%2BD1cXht1Wjt73OCrossRefGoogle Scholar
  19. 19.
    Albertini A A, Wernimont A K, Muziol T, et al. Crystal structure of the rabies virus nucleoprotein-RNA complex. Science, 2006, 313: 360–363, 16778023, 10.1126/science.1125280, 1:CAS:528:DC%2BD28XmvFyqsbg%3DCrossRefGoogle Scholar
  20. 20.
    Green T J, Zhang X, Wertz G W, et al. Structure of the vesicular stomatitis virus nucleoprotein-RNA complex. Science, 2006, 313: 357–360, 16778022, 10.1126/science.1126953, 1:CAS:528:DC%2BD28XmvFyqsbs%3DCrossRefGoogle Scholar
  21. 21.
    Luo M, Green T J, Zhang X, et al. Structural comparisons of the nucleoprotein from three negative strand RNA virus families. Virol J, 2007, 4: 72, 17623082, 10.1186/1743-422X-4-72, 1:CAS:528:DC%2BD1cXkt1Kmu7w%3DCrossRefGoogle Scholar
  22. 22.
    Willard L, Ranjan A, Zhang H, et al. VADAR: a web server for quantitative evaluation of protein structure quality. Nucleic Acids Res, 2003, 31: 3316–3319, 12824316, 10.1093/nar/gkg565, 1:CAS:528:DC%2BD3sXltVWjtb8%3DCrossRefGoogle Scholar
  23. 23.
    Faure G, Bornot A, de Brevern A G. Protein contacts, inter-residue interactions and side-chain modelling. Biochimie, 2008, 90: 626–639, 18086572, 10.1016/j.biochi.2007.11.007, 1:CAS:528:DC%2BD1cXksValsbs%3DCrossRefGoogle Scholar
  24. 24.
    Janin J, Bahadur R P, Chakrabarti P. Protein-protein interaction and quaternary structure. Quart Rev Biophy, 2008, 41: 133–180, 1:CAS:528:DC%2BD1cXhtFKhurnNCrossRefGoogle Scholar
  25. 25.
    Elton D, Medcalf E, Bishop K, et al. Oligomerization of the influenza virus nucleoprotein: identification of positive and negative sequence elements. Virology, 1999, 260: 190–200, 10405371, 10.1006/viro.1999.9818, 1:CAS:528:DyaK1MXktlynsbw%3DCrossRefGoogle Scholar
  26. 26.
    Ruigrok R W, Baudin F. Structure of influenza virus ribonucleoprotein particles. II. Purified RNA-free influenza virus ribonucleoprotein forms structures that are indistinguishable from the intact influenza virus ribonucleoprotein particles. J Gen Virol, 1995, 76: 1009–1014, 9049350, 10.1099/0022-1317-76-4-1009, 1:CAS:528:DyaK2MXksl2nsrk%3DCrossRefGoogle Scholar
  27. 27.
    Martin-Benito J, Area E, Ortega J, et al. Three-dimensional reconstruction of a recombinant influenza virus ribonucleoprotein particle. EMBO Rep, 2001, 2: 313–317, 11306552, 10.1093/embo-reports/kve063, 1:CAS:528:DC%2BD3MXks1Cqtbg%3DCrossRefGoogle Scholar
  28. 28.
    Baudin F, Bach C, Cusack S, et al. Structure of influenza virus RNP. I. Influenza virus nucleoprotein melts secondary structure in panhandle RNA and exposes the bases to the solvent. EMBO J, 1994, 13: 3158–3165, 8039508, 1:CAS:528:DyaK2cXlt12mtrk%3DGoogle Scholar
  29. 29.
    Yamanaka K, Ishihama A, Nagata K. Reconstitution of influenza virus RNA-nucleoprotein complexes structurally resembling native viral ribonucleoprotein cores. J Biol Chem, 1990, 265: 11151–11155, 2358455, 1:CAS:528:DyaK3cXkslCntrw%3DGoogle Scholar
  30. 30.
    Elton D, Medcalf L, Bishop K, et al. Identification of amino acid residues of influenza virus nucleoprotein essential for RNA binding. J Virol, 1999, 73: 7357–7367, 10438825, 1:CAS:528:DyaK1MXltlKhtr4%3DGoogle Scholar
  31. 31.
    Medcalf L, Poole E, Elton D, et al. Temperature-sensitive lesions in two influenza A viruses defective for replicative transcription disrupt RNA binding by the nucleoprotein. J Virol, 1999, 73: 7349–7356, 10438824, 1:CAS:528:DyaK1MXltlKhsbc%3DGoogle Scholar
  32. 32.
    Area E, Martin-Benito J, Gastaminza P, et al. 3D structure of the influenza virus polymerase complex: localization of subunit domains. Proc Natl Acad Sci USA, 2004, 101: 308–313, 14691253, 10.1073/pnas.0307127101, 1:CAS:528:DC%2BD2cXjvFamug%3D%3DCrossRefGoogle Scholar
  33. 33.
    Doolittle R F. Redundancies in protein sequences. In Prediction of Protein Structure and the Principles of Protein Conformation (Fasman, GD, ed) Plenum Press, NY, 1989, 599–623CrossRefGoogle Scholar
  34. 34.
    Li Z, Watanabe T, Hatta M, et al. Mutational analysis of conserved amino acids in the influenza A virus nucleoprotein. J Virol, 2009, 83: 4153–4162, 19225007, 10.1128/JVI.02642-08, 1:CAS:528:DC%2BD1MXlt1Kqtbw%3DCrossRefGoogle Scholar
  35. 35.
    Zhang K, Sun F. Assessing the power of tag SNPs in the mapping of quantitative trait loci (QTL) with extremal and random samples. BMC Genet, 2005, 6: 51, 16236175, 10.1186/1471-2156-6-51, 1:CAS:528:DC%2BD28XhtFKisrnJCrossRefGoogle Scholar
  36. 36.
    Albo C, Valencia A, Portela A. Identification of an RNA binding region within the N-terminal third of the influenza A virus nucleoprotein. J Virol, 1995, 69: 3799–3806, 7745727, 1:CAS:528:DyaK2MXls1yiu7w%3DGoogle Scholar

Copyright information

© Science in China Press and Springer-Verlag GmbH 2009

Authors and Affiliations

  • Andy Ka-Leung Ng
    • 1
  • Jia-Huai Wang
    • 2
  • Pang-Chui Shaw
    • 1
  1. 1.Molecular Biotechnology Programme, Department of Biochemistry and Centre for Protein Science and CrystallographyThe Chinese University of Hong KongShatin, Hong Kong SARChina
  2. 2.Dana-Farber Cancer Institute, Department of Pediatrics, Department of Biological Chemistry and Molecular PharmacologyHarvard Medical SchoolBostonUSA

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