Structure and Function of Influenza Virus Ribonucleoprotein

  • Chun-Yeung Lo
  • Yun-Sang Tang
  • Pang-Chui ShawEmail author
Part of the Subcellular Biochemistry book series (SCBI, volume 88)


Influenza is a negative-sense single-stranded RNA virus with segmented genome. Each segment is encapsidated by a ribonucleoprotein (RNP) complex composed of RNA-dependent RNA polymerase (RdRP) and multiple copies of nucleoprotein (NP). The RNP complex plays a crucial role in viral life cycle, supporting and regulating transcription and replication of viral genome in infected cells. The structural characterization of RdRP and RNP in recent years has shed light on its functions and mechanism of action. In this review, we summarize current understanding on the structure of RNP complex, as well as the structure of each subunit. Crucial functions of RNP are also discussed.


Influenza RNA-dependent RNA polymerase Ribonucleoprotein PA PB1 PB2 Nucleoprotein Viral transcription and replication 


  1. Appleby TC, Perry JK, Murakami E et al (2015) Structural basis for RNA replication by the hepatitis C virus polymerase. Science 347:771–775PubMedGoogle Scholar
  2. Area E, Martín-Benito J, Gastaminza P et al (2004) 3D structure of the influenza virus polymerase complex: localization of subunit domains. Proc Natl Acad Sci U S A 101:308–313PubMedGoogle Scholar
  3. Arranz R, Coloma R, Chichón FJ et al (2012) The structure of native influenza virion ribonucleoproteins. Science 338:1634–1637PubMedGoogle Scholar
  4. Biswas SK, Nayak DP (1994) Mutational analysis of the conserved motifs of influenza a virus polymerase basic protein 1. J Virol 68:1819–1826PubMedPubMedCentralGoogle Scholar
  5. Brownlee GG, Sharps JL (2002) The RNA polymerase of influenza a virus is stabilized by interaction with its viral RNA promoter. J Virol 76:7103–7113PubMedPubMedCentralGoogle Scholar
  6. Butcher SJ, Grimes JM, Makeyev EV et al (2001) A mechanism for initiating RNA-dependent RNA polymerization. Nature 410:235–240PubMedGoogle Scholar
  7. Caillet-Saguy C, Lim SP, Shi P-Y et al (2014) Polymerases of hepatitis C viruses and flaviviruses: structural and mechanistic insights and drug development. Antivir Res 105:8–16PubMedGoogle Scholar
  8. Chang S, Sun D, Liang H et al (2015) Cryo-EM structure of influenza virus RNA polymerase complex at 4.3 Å resolution. Mol Cell 57:925–935PubMedGoogle Scholar
  9. Chenavas S, Crépin T, Delmas B et al (2013a) Influenza virus nucleoprotein: structure, RNA binding, oligomerization and antiviral drug target. Future Microbiol 8:1537–1545PubMedGoogle Scholar
  10. Chenavas S, Estrozi LF, Slama-Schwok A et al (2013b) Monomeric nucleoprotein of influenza a virus. PLoS Pathog 9:e1003275PubMedPubMedCentralGoogle Scholar
  11. Coloma R, Valpuesta JM, Arranz R et al (2009) The structure of a biologically active influenza virus ribonucleoprotein complex. PLoS Pathog 5:e1000491PubMedPubMedCentralGoogle Scholar
  12. Compans RW, Content J, Duesberg PH (1972) Structure of the ribonucleoprotein of influenza virus. J Virol 10:795–800PubMedPubMedCentralGoogle Scholar
  13. Crepin T, Dias A, Palencia A et al (2010) Mutational and metal binding analysis of the endonuclease domain of the influenza virus polymerase PA subunit. J Virol 84:9096–9104PubMedPubMedCentralGoogle Scholar
  14. Datta K, Wolkerstorfer A, Szolar OHJ et al (2013) Characterization of PA-N terminal domain of influenza a polymerase reveals sequence specific RNA cleavage. Nucleic Acids Res 41:8289–8299PubMedPubMedCentralGoogle Scholar
  15. Deng T, Sharps J, Fodor E, Brownlee GG (2005) In vitro assembly of PB2 with a PB1-PA dimer supports a new model of assembly of influenza a virus polymerase subunits into a functional trimeric complex. J Virol 79:8669–8674PubMedPubMedCentralGoogle Scholar
  16. Deng T, Vreede FT, Brownlee GG (2006) Different de novo initiation strategies are used by influenza virus RNA polymerase on its cRNA and viral RNA promoters during viral RNA replication. J Virol 80:2337–2348PubMedPubMedCentralGoogle Scholar
  17. Dias A, Bouvier D, Crépin T et al (2009) The cap-snatching endonuclease of influenza virus polymerase resides in the PA subunit. Nature 458:914–918PubMedGoogle Scholar
  18. Doan L, Handa B, Roberts NA, Klumpp K (1999) Metal ion catalysis of RNA cleavage by the influenza virus endonuclease. Biochemistry 38:5612–5619PubMedGoogle Scholar
  19. DuBois RM, Slavish PJ, Baughman BM et al (2012) Structural and biochemical basis for development of influenza virus inhibitors targeting the PA endonuclease. PLoS Pathog 8:e1002830PubMedPubMedCentralGoogle Scholar
  20. Eisfeld AJ, Neumann G, Kawaoka Y (2014) At the centre: influenza a virus ribonucleoproteins. Nat Rev Microbiol 13:28–41PubMedPubMedCentralGoogle Scholar
  21. Engelhardt OG, Smith M, Fodor E (2005) Association of the influenza a virus RNA-dependent RNA polymerase with cellular RNA polymerase II. J Virol 79:5812–5818PubMedPubMedCentralGoogle Scholar
  22. Flick R, Neumann G, Hoffmann E et al (1996) Promoter elements in the influenza vRNA terminal structure. RNA 2:1046–1057PubMedPubMedCentralGoogle Scholar
  23. Geerts-Dimitriadou C, Goldbach R, Kormelink R (2011a) Preferential use of RNA leader sequences during influenza a transcription initiation in vivo. Virology 409:27–32PubMedGoogle Scholar
  24. Geerts-Dimitriadou C, Zwart MP, Goldbach R, Kormelink R (2011b) Base-pairing promotes leader selection to prime in vitro influenza genome transcription. Virology 409:17–26PubMedGoogle Scholar
  25. González S, Ortín J (1999a) Characterization of influenza virus PB1 protein binding to viral RNA: two separate regions of the protein contribute to the interaction domain. J Virol 73:631–637PubMedPubMedCentralGoogle Scholar
  26. González S, Ortín J (1999b) Distinct regions of influenza virus PB1 polymerase subunit recognize vRNA and cRNA templates. EMBO J 18:3767–3775PubMedPubMedCentralGoogle Scholar
  27. González S, Zürcher T, Ortín J (1996) Identification of two separate domains in the influenza virus PB1 protein involved in the interaction with the PB2 and PA subunits: a model for the viral RNA polymerase structure. Nucleic Acids Res 24:4456–4463PubMedPubMedCentralGoogle Scholar
  28. Gu W, Gallagher GR, Dai W et al (2015) Influenza a virus preferentially snatches noncoding RNA caps. RNA 21:2067–2075PubMedPubMedCentralGoogle Scholar
  29. Guilligay D, Tarendeau F, Resa-Infante P et al (2008) The structural basis for cap binding by influenza virus polymerase subunit PB2. Nat Struct Mol Biol 15:500–506PubMedGoogle Scholar
  30. Guu TSY, Dong L, Wittung-Stafshede P, Tao YJ (2008) Mapping the domain structure of the influenza a virus polymerase acidic protein (PA) and its interaction with the basic protein 1 (PB1) subunit. Virology 379:135–142PubMedGoogle Scholar
  31. Hara K, Kashiwagi T, Hamada N, Watanabe H (2017) Basic amino acids in the N-terminal half of the PB2 subunit of influenza virus RNA polymerase are involved in both transcription and replication. J Gen Virol 98:900–905PubMedGoogle Scholar
  32. He X, Zhou J, Bartlam M et al (2008) Crystal structure of the polymerase PAC–PB1N complex from an avian influenza H5N1 virus. Nature 454:1123–1126PubMedGoogle Scholar
  33. Hengrung N, El Omari K, Serna Martin I et al (2015) Crystal structure of the RNA-dependent RNA polymerase from influenza C virus. Nature 527:114–117PubMedPubMedCentralGoogle Scholar
  34. Hobom G, Flick R (1999) Interaction of influenza virus polymerase with viral RNA in the “corkscrew” conformation. J Gen Virol 80:2565–2572PubMedGoogle Scholar
  35. Hsia H-P, Yang Y-H, Szeto W-C, Nilsson BE, Lo C-Y, Ng AK-L, Fodor E, Shaw P-C, Menéndez-Arias L (2018) Amino acid substitutions affecting aspartic acid 605 and valine 606 decrease the interaction strength between the influenza virus RNA polymerase PB2 ‘627’ domain and the viral nucleoprotein. PLOS ONE 13(1):e0191226PubMedPubMedCentralGoogle Scholar
  36. Huet S, Avilov SV, Ferbitz L et al (2010) Nuclear import and assembly of influenza a virus RNA polymerase studied in live cells by fluorescence cross-correlation spectroscopy. J Virol 84:1254–1264PubMedGoogle Scholar
  37. Jorba N, Area E, Ortin J (2008) Oligomerization of the influenza virus polymerase complex in vivo. J Gen Virol 89:520–524PubMedGoogle Scholar
  38. Jorba N, Coloma R, Ortín J (2009) Genetic trans-complementation establishes a new model for influenza virus RNA transcription and replication. PLoS Pathog 5:e1000462PubMedPubMedCentralGoogle Scholar
  39. Jung TE, Brownlee GG (2006) A new promoter-binding site in the PB1 subunit of the influenza a virus polymerase. J Gen Virol 87:679–688PubMedGoogle Scholar
  40. Koppstein D, Ashour J, Bartel DP (2015) Sequencing the cap-snatching repertoire of H1N1 influenza provides insight into the mechanism of viral transcription initiation. Nucleic Acids Res 43:5052–5064PubMedPubMedCentralGoogle Scholar
  41. Kotlarek D, Worch R (2016) New insight into metal ion-driven catalysis of nucleic acids by influenza PA-Nter. PLoS One 11:e0156972PubMedPubMedCentralGoogle Scholar
  42. Kuzuhara T, Kise D, Yoshida H et al (2009) Structural basis of the influenza a virus RNA polymerase PB2 RNA-binding domain containing the pathogenicity-determinant lysine 627 residue. J Biol Chem 284:6855–6860PubMedPubMedCentralGoogle Scholar
  43. Lee MTM, Bishop K, Medcalf L et al (2002) Definition of the minimal viral components required for the initiation of unprimed RNA synthesis by influenza virus RNA polymerase. Nucleic Acids Res 30:429–438PubMedPubMedCentralGoogle Scholar
  44. Lee M-TM, Klumpp K, Digard P, Tiley L (2003) Activation of influenza virus RNA polymerase by the 5′ and 3′ terminal duplex of genomic RNA. Nucleic Acids Res 31:1624–1632PubMedPubMedCentralGoogle Scholar
  45. Li M-L, Ramirez BC, Krug RM (1998) RNA-dependent activation of primer RNA production by influenza virus polymerase: different regions of the same protein subunit constitute the two required RNA-binding sites. EMBO J 17:5844–5852PubMedPubMedCentralGoogle Scholar
  46. Li M-L, Rao P, Krug RM (2001) The active sites of the influenza cap-dependent endonuclease are on different polymerase subunits. EMBO J 20:2078–2086PubMedPubMedCentralGoogle Scholar
  47. Liu Y, Qin K, Meng G et al (2013) Structural and functional characterization of K339T substitution identified in the PB2 subunit cap-binding pocket of influenza a virus. J Biol Chem 288:11013–11023PubMedPubMedCentralGoogle Scholar
  48. Liu M, Lam MK-H, Zhang Q et al (2015a) The functional study of the N-terminal region of influenza B virus nucleoprotein. PLoS One 10:e0137802PubMedPubMedCentralGoogle Scholar
  49. Liu Y, Yang Y, Fan J et al (2015b) The crystal structure of the PB2 cap-binding domain of influenza B virus reveals a novel cap recognition mechanism. J Biol Chem 290:9141–9149PubMedPubMedCentralGoogle Scholar
  50. Lukarska M, Fournier G, Pflug A et al (2017) Structural basis of an essential interaction between influenza polymerase and pol II CTD. Nature 541:117–121PubMedGoogle Scholar
  51. Martín-Benito J, Area E, Ortega J et al (2001) Three-dimensional reconstruction of a recombinant influenza virus ribonucleoprotein particle. EMBO Rep 2:313–317PubMedPubMedCentralGoogle Scholar
  52. Martínez-Alonso M, Hengrung N, Fodor E (2016) RNA-free and ribonucleoprotein-associated influenza virus polymerases directly bind the Serine-5-phosphorylated carboxyl-terminal domain of host RNA polymerase II. J Virol 90:6014–6021PubMedPubMedCentralGoogle Scholar
  53. Moeller A, Kirchdoerfer RN, Potter CS et al (2012) Organization of the influenza virus replication machinery. Science 338:1631–1634PubMedPubMedCentralGoogle Scholar
  54. Moen SO, Abendroth J, Fairman JW et al (2014) Structural analysis of H1N1 and H7N9 influenza a virus PA in the absence of PB1. Sci Rep 4:5944Google Scholar
  55. Murti KG, Webster RG, Jones IM (1988) Localization of RNA polymerases on influenza viral ribonucleoproteins by immunogold labeling. Virology 164:562–566PubMedGoogle Scholar
  56. Nakada R, Hirano H, Matsuura Y (2015) Structure of importin-alpha bound to a non-classical nuclear localization signal of the influenza a virus nucleoprotein. Sci Rep 5:15055PubMedPubMedCentralGoogle Scholar
  57. Ng AK-L, Zhang H, Tan K et al (2008) Structure of the influenza virus a H5N1 nucleoprotein: implications for RNA binding, oligomerization, and vaccine design. FASEB J 22:3638–3647PubMedPubMedCentralGoogle Scholar
  58. Ng AK-L, Wang J-H, Shaw P-C (2009) Structure and sequence analysis of influenza a virus nucleoprotein. Sci China Ser C Life Sci 52:439–449Google Scholar
  59. Ng AK-L, Lam MK-H, Zhang H et al (2012) Structural basis for RNA binding and homo-oligomer formation by influenza B virus nucleoprotein. J Virol 86:6758–6767PubMedPubMedCentralGoogle Scholar
  60. Nilsson BE, te Velthuis AJW, Fodor E (2017) Role of the PB2 627 domain in influenza a virus polymerase function. J Virol 91:e02467-16–e02e02467PubMedPubMedCentralGoogle Scholar
  61. Noda T, Sagara H, Yen A et al (2006) Architecture of ribonucleoprotein complexes in influenza a virus particles. Nature 439:490–492PubMedGoogle Scholar
  62. Obayashi E, Yoshida H, Kawai F et al (2008) The structural basis for an essential subunit interaction in influenza virus RNA polymerase. Nature 454:1127–1131PubMedGoogle Scholar
  63. Ohtsu Y, Honda Y, Sakata Y et al (2002) Fine mapping of the subunit binding sites of influenza virus RNA polymerase. Microbiol Immunol 46:167–175PubMedGoogle Scholar
  64. Oymans J, te Velthuis A (2017) Correct And efficient initiation of viral RNA synthesis by the influenza A virus RNA polymerase bioRvix 138487Google Scholar
  65. Perez DR, Donis RO (2001) Functional analysis of PA binding by influenza a virus PB1: effects on polymerase activity and viral infectivity. J Virol 75:8127–8136PubMedPubMedCentralGoogle Scholar
  66. Pflug A, Guilligay D, Reich S, Cusack S (2014) Structure of influenza a polymerase bound to the viral RNA promoter. Nature 516:355–360PubMedPubMedCentralGoogle Scholar
  67. Pons MW, Schulze IT, Hirst GK, Hauser R (1969) Isolation and characterization of the ribonucleoprotein of influenza virus. Virology 39:250–259PubMedGoogle Scholar
  68. Poon LL, Pritlove DC, Fodor E, Brownlee GG (1999) Direct evidence that the poly(A) tail of influenza A virus mRNA is synthesized by reiterative copying of a U track in the virion RNA template. J Virol 73:3473–3476PubMedPubMedCentralGoogle Scholar
  69. Poon LL, Fodor E, Brownlee GG (2000) Polyuridylated mRNA synthesized by a recombinant influenza virus is defective in nuclear export. J Virol 74:418–427PubMedPubMedCentralGoogle Scholar
  70. Pritlove DC, Poon LL, Fodor E et al (1998) Polyadenylation of influenza virus mRNA transcribed in vitro from model virion RNA templates: requirement for 5′ conserved sequences. J Virol 72:1280–1286PubMedPubMedCentralGoogle Scholar
  71. Pumroy RAA, Ke S, Hart DJJ et al (2015) Molecular determinants for nuclear import of influenza a PB2 by importin α isoforms 3 and 7. Structure 23:374–384PubMedPubMedCentralGoogle Scholar
  72. Rao P, Yuan W, Krug RM (2003) Crucial role of CA cleavage sites in the cap-snatching mechanism for initiating viral mRNA synthesis. EMBO J 22:1188–1198PubMedPubMedCentralGoogle Scholar
  73. Reguera J, Gerlach P, Cusack S (2016) Towards a structural understanding of RNA synthesis by negative strand RNA viral polymerases. Curr Opin Struct Biol 36:75–84PubMedGoogle Scholar
  74. Reich S, Guilligay D, Pflug A et al (2014) Structural insight into cap-snatching and RNA synthesis by influenza polymerase. Nature 516:361–366PubMedGoogle Scholar
  75. Reich S, Guilligay D, Cusack S (2017) An in vitro fluorescence based study of initiation of RNA synthesis by influenza B polymerase. Nucleic Acids Res 45:3353–3368PubMedPubMedCentralGoogle Scholar
  76. Resa-Infante P, Recuero-Checa MA, Zamarreño N et al (2010) Structural and functional characterization of an influenza virus RNA polymerase-genomic RNA complex. J Virol 84:10477–10487PubMedPubMedCentralGoogle Scholar
  77. Ruigrok RW, Baudin F (1995) 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 76(Pt 4):1009–1014PubMedGoogle Scholar
  78. Sikora D, Rocheleau L, Brown EG, Pelchat M (2014) Deep sequencing reveals the eight facets of the influenza a/HongKong/1/1968 (H3N2) virus cap-snatching process. Sci Rep 4:6181PubMedPubMedCentralGoogle Scholar
  79. Sugiyama K, Obayashi E, Kawaguchi A et al (2009) Structural insight into the essential PB1-PB2 subunit contact of the influenza virus RNA polymerase. EMBO J 28:1803–1811PubMedPubMedCentralGoogle Scholar
  80. Swale C, Monod A, Tengo L et al (2016) Structural characterization of recombinant IAV polymerase reveals a stable complex between viral PA-PB1 heterodimer and host RanBP5. Sci Rep 6:24727PubMedPubMedCentralGoogle Scholar
  81. Tao Y, Farsetta DL, Nibert ML, Harrison SC (2002) RNA synthesis in a cage-structural studies of reovirus polymerase lambda3. Cell 111:733–745PubMedGoogle Scholar
  82. Tarendeau F, Boudet J, Guilligay D et al (2007) Structure and nuclear import function of the C-terminal domain of influenza virus polymerase PB2 subunit. Nat Struct Mol Biol 14:229–233PubMedGoogle Scholar
  83. Tarendeau F, Crepin T, Guilligay D et al (2008) Host determinant residue lysine 627 lies on the surface of a discrete, folded domain of influenza virus polymerase PB2 subunit. PLoS Pathog 4:e1000136PubMedPubMedCentralGoogle Scholar
  84. Thierry E, Guilligay D, Kosinski J et al (2016) Influenza polymerase can adopt an alternative configuration involving a radical repacking of PB2 domains. Mol Cell 61:125–137PubMedPubMedCentralGoogle Scholar
  85. Tomescu AI, Robb NC, Hengrung N et al (2014) Single-molecule FRET reveals a corkscrew RNA structure for the polymerase-bound influenza virus promoter. Proc Natl Acad Sci U S A 111:E3335–E3342PubMedPubMedCentralGoogle Scholar
  86. Torreira E, Schoehn G, Fernández Y et al (2007) Three-dimensional model for the isolated recombinant influenza virus polymerase heterotrimer. Nucleic Acids Res 35:3774–3783PubMedPubMedCentralGoogle Scholar
  87. Tsurumura T, Qiu H, Yoshida T et al (2013) Conformational polymorphism of m7GTP in crystal structure of the PB2 middle domain from human influenza a virus. PLoS One 8:e82020PubMedPubMedCentralGoogle Scholar
  88. te Velthuis AJW, Fodor E (2016) Influenza virus RNA polymerase: insights into the mechanisms of viral RNA synthesis. Nat Rev Microbiol 14:479–493Google Scholar
  89. te Velthuis AJW, Robb NC, Kapanidis AN et al (2016) The role of the priming loop in influenza a virus RNA synthesis. Nat Microbiol 1:16029Google Scholar
  90. Vreede FT, Brownlee GG (2007) Influenza virion-derived viral ribonucleoproteins synthesize both mRNA and cRNA in vitro. J Virol 81:2196–2204PubMedGoogle Scholar
  91. Vreede FT, Jung TE, Brownlee GG (2004) Model suggesting that replication of influenza virus is regulated by stabilization of replicative intermediates. J Virol 78:9568–9572PubMedPubMedCentralGoogle Scholar
  92. Wakai C, Iwama M, Mizumoto K, Nagata K (2011) Recognition of cap structure by influenza B virus RNA polymerase is less dependent on the methyl residue than recognition by influenza a virus polymerase. J Virol 85:7504–7512PubMedPubMedCentralGoogle Scholar
  93. Wunderlich K, Juozapaitis M, Ranadheera C et al (2011) Identification of high-affinity PB1-derived peptides with enhanced affinity to the PA protein of influenza a virus polymerase. Antimicrob Agents Chemother 55:696–702PubMedGoogle Scholar
  94. Xiao S, Klein ML, LeBard DN et al (2014) Magnesium-dependent RNA binding to the PA endonuclease domain of the avian influenza polymerase. J Phys Chem B 118:873–889PubMedGoogle Scholar
  95. Xie L, Wartchow C, Shia S et al (2016) Molecular basis of mRNA cap recognition by influenza B polymerase PB2 subunit. J Biol Chem 291:363–370PubMedGoogle Scholar
  96. Yamada S, Hatta M, Staker BL et al (2010) Biological and structural characterization of a host-adapting amino acid in influenza virus. PLoS Pathog 6:e1001034PubMedPubMedCentralGoogle Scholar
  97. Yamanaka K, Ishihama A, Nagata K (1990) Reconstitution of influenza virus RNA-nucleoprotein complexes structurally resembling native viral ribonucleoprotein cores. J Biol Chem 265:11151–11155PubMedGoogle Scholar
  98. Yang Y, Tang Y-S, Shaw P-C (2014) Structure and function of nucleoprotein from Orthomyxoviruses. Biodesign 2:91–99Google Scholar
  99. Ye Q, Krug RM, Tao YJ (2006) The mechanism by which influenza a virus nucleoprotein forms oligomers and binds RNA. Nature 444:1078–1082PubMedGoogle Scholar
  100. Ye Q, Guu TSY, Mata DA et al (2012) Biochemical and structural evidence in support of a coherent model for the formation of the double-helical influenza a virus ribonucleoprotein. MBio 4:e00467–e00412PubMedPubMedCentralGoogle Scholar
  101. York A, Hengrung N, Vreede FT et al (2013) Isolation and characterization of the positive-sense replicative intermediate of a negative-strand RNA virus. Proc Natl Acad Sci 110(45):E4238PubMedGoogle Scholar
  102. Yuan P, Bartlam M, Lou Z et al (2009) Crystal structure of an avian influenza polymerase PAN reveals an endonuclease active site. Nature 458:909–913PubMedGoogle Scholar
  103. Zhang S, Wang J, Wang Q, Toyoda T (2010) Internal initiation of influenza virus replication of viral RNA and complementary RNA in Vitro. J Biol Chem 285:41194–41201PubMedPubMedCentralGoogle Scholar
  104. Zhao C, Lou Z, Guo Y et al (2009) Nucleoside monophosphate complex structures of the endonuclease domain from the influenza virus polymerase PA subunit reveal the substrate binding site inside the catalytic center. J Virol 83:9024–9030PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  1. 1.Centre for Protein Science and Crystallography, School of Life SciencesThe Chinese University of Hong KongShatinChina

Personalised recommendations