Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Structure of influenza A polymerase bound to the viral RNA promoter

Nature volume 516, pages 355–360 (2014)Cite this article

Subjects

Abstract

The influenza virus polymerase transcribes or replicates the segmented RNA genome (viral RNA) into viral messenger RNA or full-length copies. To initiate RNA synthesis, the polymerase binds to the conserved 3′ and 5′ extremities of the viral RNA. Here we present the crystal structure of the heterotrimeric bat influenza A polymerase, comprising subunits PA, PB1 and PB2, bound to its viral RNA promoter. PB1 contains a canonical RNA polymerase fold that is stabilized by large interfaces with PA and PB2. The PA endonuclease and the PB2 cap-binding domain, involved in transcription by cap-snatching, form protrusions facing each other across a solvent channel. The 5′ extremity of the promoter folds into a compact hook that is bound in a pocket formed by PB1 and PA close to the polymerase active site. This structure lays the basis for an atomic-level mechanistic understanding of the many functions of influenza polymerase, and opens new opportunities for anti-influenza drug design.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Get just this article for as long as you need it

$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Overall structure of the bat influenza A polymerase complex with the vRNA promoter.
Figure 2: PB1 structure and comparison with other RNA virus polymerases.
Figure 3: PA and PB2 structure and the PA-linker–PB1 interface.
Figure 4: PB1 functional regions.
Figure 5: Structure of the vRNA promoter and how it binds to the polymerase.

Accession codes

Primary accessions

Protein Data Bank

Data deposits

Structure factors and coordinates for Bat FluA have been deposited in the Protein Data Bank (PDB) under accession 4WSB.

References

  1. Resa-Infante, P., Jorba, N., Coloma, R. & Ortin, J. The influenza virus RNA synthesis machine: advances in its structure and function. RNA Biol. 8, 207–215 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Fodor, E. The RNA polymerase of influenza a virus: mechanisms of viral transcription and replication. Acta Virol. 57, 113–122 (2013)

    Article  CAS  PubMed  Google Scholar 

  3. Ruigrok, R. W., Crepin, T., Hart, D. J. & Cusack, S. Towards an atomic resolution understanding of the influenza virus replication machinery. Curr. Opin. Struct. Biol. 20, 104–113 (2010)

    Article  CAS  PubMed  Google Scholar 

  4. Plotch, S. J., Bouloy, M., Ulmanen, I. & Krug, R. M. A unique cap(m7GpppXm)-dependent influenza virion endonuclease cleaves capped RNAs to generate the primers that initiate viral RNA transcription. Cell 23, 847–858 (1981)

    Article  CAS  PubMed  Google Scholar 

  5. Dias, A. et al. The cap-snatching endonuclease of influenza virus polymerase resides in the PA subunit. Nature 458, 914–918 (2009)

    Article  ADS  CAS  PubMed  Google Scholar 

  6. Yuan, P. et al. Crystal structure of an avian influenza polymerase PAN reveals an endonuclease active site. Nature 458, 909–913 (2009)

    Article  ADS  CAS  PubMed  Google Scholar 

  7. Guilligay, D. et al. The structural basis for cap binding by influenza virus polymerase subunit PB2. Nature Struct. Mol. Biol. 15, 500–506 (2008)

    Article  CAS  Google Scholar 

  8. Kowalinski, E. et al. Structural analysis of specific metal chelating inhibitor binding to the endonuclease domain of influenza pH1N1 (2009) polymerase. PLoS Pathog. 8, e1002831 (2012)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Clark, M. P. et al. Discovery of a novel, first-in-class, orally bioavailable azaindole inhibitor (VX-787) of influenza PB2. J. Med. Chem. 57, 6668–6678 (2014)

    Article  CAS  PubMed  Google Scholar 

  10. He, X. et al. Crystal structure of the polymerase PAC–PB1N complex from an avian influenza H5N1 virus. Nature 454, 1123–1126 (2008)

    Article  ADS  CAS  PubMed  Google Scholar 

  11. Obayashi, E. et al. The structural basis for an essential subunit interaction in influenza virus RNA polymerase. Nature 454, 1127–1131 (2008)

    Article  ADS  CAS  PubMed  Google Scholar 

  12. Sugiyama, K. et al. Structural insight into the essential PB1–PB2 subunit contact of the influenza virus RNA polymerase. EMBO J. 28, 1803–1811 (2009)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Tarendeau, F. et al. Host determinant residue lysine 627 lies on the surface of a discrete, folded domain of influenza virus polymerase PB2 subunit. PLoS Pathog. 4, e1000136 (2008)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Cauldwell, A. V., Long, J. S., Moncorge, O. & Barclay, W. S. Viral determinants of influenza A virus host range. J. Gen. Virol. 95, 1193–1210 (2014)

    Article  CAS  PubMed  Google Scholar 

  15. Tarendeau, F. et al. Structure and nuclear import function of the C-terminal domain of influenza virus polymerase PB2 subunit. Nature Struct. Mol. Biol. 14, 229–233 (2007)

    Article  CAS  Google Scholar 

  16. Tong, S. et al. A distinct lineage of influenza A virus from bats. Proc. Natl Acad. Sci. USA 109, 4269–4274 (2012)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  17. Poole, D. S. et al. Influenza A virus polymerase is a site for adaptive changes during experimental evolution in bat cells. J. Virol. 88, 12572–12585 (2014)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Reich, S. et al. Structural insights into cap-snatching and RNA synthesis by influenza virus polymerase. Nature http://dx.doi.org/10.1038/nature14009 (this issue)

  19. Turrell, L., Lyall, J. W., Tiley, L. S., Fodor, E. & Vreede, F. T. The role and assembly mechanism of nucleoprotein in influenza A virus ribonucleoprotein complexes. Nature Commun. 4, 1591 (2013)

    Article  ADS  CAS  Google Scholar 

  20. González, S., Zurcher, T. & Ortin, J. 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, 4456–4463 (1996)

    Article  PubMed  PubMed Central  Google Scholar 

  21. Poole, E. L., Medcalf, L., Elton, D. & Digard, P. Evidence that the C-terminal PB2-binding region of the influenza A virus PB1 protein is a discrete α-helical domain. FEBS Lett. 581, 5300–5306 (2007)

    Article  CAS  PubMed  Google Scholar 

  22. Müller, R., Poch, O., Delarue, M., Bishop, D. H. & Bouloy, M. Rift Valley fever virus L segment: correction of the sequence and possible functional role of newly identified regions conserved in RNA-dependent polymerases. J. Gen. Virol. 75, 1345–1352 (1994)

    Article  PubMed  Google Scholar 

  23. Biswas, S. K. & Nayak, D. P. Mutational analysis of the conserved motifs of influenza A virus polymerase basic protein 1. J. Virol. 68, 1819–1826 (1994)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Bruenn, J. A. A structural and primary sequence comparison of the viral RNA-dependent RNA polymerases. Nucleic Acids Res. 31, 1821–1829 (2003)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Yap, T. L. et al. Crystal structure of the dengue virus RNA-dependent RNA polymerase catalytic domain at 1.85-angstrom resolution. J. Virol. 81, 4753–4765 (2007)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Lesburg, C. A. et al. Crystal structure of the RNA-dependent RNA polymerase from hepatitis C virus reveals a fully encircled active site. Nature Struct. Biol. 6, 937–943 (1999)

    Article  CAS  PubMed  Google Scholar 

  27. Bressanelli, S. et al. Crystal structure of the RNA-dependent RNA polymerase of hepatitis C virus. Proc. Natl Acad. Sci. USA 96, 13034–13039 (1999)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  28. Butcher, S. J., Grimes, J. M., Makeyev, E. V., Bamford, D. H. & Stuart, D. I. A mechanism for initiating RNA-dependent RNA polymerization. Nature 410, 235–240 (2001)

    Article  ADS  CAS  PubMed  Google Scholar 

  29. Caillet-Saguy, C., Lim, S. P., Shi, P. Y., Lescar, J. & Bressanelli, S. Polymerases of hepatitis C viruses and flaviviruses: structural and mechanistic insights and drug development. Antiviral Res. 105, 8–16 (2014)

    Article  CAS  PubMed  Google Scholar 

  30. Hutchinson, E. C., Orr, O. E., Man Liu, S., Engelhardt, O. G. & Fodor, E. Characterization of the interaction between the influenza A virus polymerase subunit PB1 and the host nuclear import factor Ran-binding protein 5. J. Gen. Virol. 92, 1859–1869 (2011)

    Article  CAS  PubMed  Google Scholar 

  31. Kuzuhara, T. et al. Structural basis of the influenza A virus RNA polymerase PB2 RNA-binding domain containing the pathogenicity-determinant lysine 627 residue. J. Biol. Chem. 284, 6855–6860 (2009)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Pautus, S. et al. New 7-methylguanine derivatives targeting the influenza polymerase PB2 cap-binding domain. J. Med. Chem. 56, 8915–8930 (2013)

    Article  CAS  PubMed  Google Scholar 

  33. Zamyatkin, D. F. et al. Structural insights into mechanisms of catalysis and inhibition in Norwalk virus polymerase. J. Biol. Chem. 283, 7705–7712 (2008)

    Article  CAS  PubMed  Google Scholar 

  34. Fodor, E., Pritlove, D. C. & Brownlee, G. G. The influenza virus panhandle is involved in the initiation of transcription. J. Virol. 68, 4092–4096 (1994)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Tiley, L. S., Hagen, M., Matthews, J. T. & Krystal, M. Sequence-specific binding of the influenza virus RNA polymerase to sequences located at the 5′ ends of the viral RNAs. J. Virol. 68, 5108–5116 (1994)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Hsu, M. T., Parvin, J. D., Gupta, S., Krystal, M. & Palese, P. 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 84, 8140–8144 (1987)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  37. Neumann, G. & Hobom, G. Mutational analysis of influenza virus promoter elements in vivo. J. Gen. Virol. 76, 1709–1717 (1995)

    Article  CAS  PubMed  Google Scholar 

  38. Flick, R., Neumann, G., Hoffmann, E., Neumeier, E. & Hobom, G. Promoter elements in the influenza vRNA terminal structure. RNA 2, 1046–1057 (1996)

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Fodor, E., Pritlove, D. C. & Brownlee, G. G. Characterization of the RNA-fork model of virion RNA in the initiation of transcription in influenza A virus. J. Virol. 69, 4012–4019 (1995)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Kim, H. J., Fodor, E., Brownlee, G. G. & Seong, B. L. Mutational analysis of the RNA-fork model of the influenza A virus vRNA promoter in vivo. J. Gen. Virol. 78, 353–357 (1997)

    Article  CAS  PubMed  Google Scholar 

  41. Pritlove, D. C., Poon, L. L., Devenish, L. J., Leahy, M. B. & Brownlee, G. G. A hairpin loop at the 5′ end of influenza A virus virion RNA is required for synthesis of poly(A)+ mRNA in vitro. J. Virol. 73, 2109–2114 (1999)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Briese, T. et al. Upolu virus and Aransas Bay virus, two presumptive bunyaviruses, are novel members of the family Orthomyxoviridae. J. Virol. 88, 5298–5309 (2014)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. Fodor, E. et al. A single amino acid mutation in the PA subunit of the influenza virus RNA polymerase inhibits endonucleolytic cleavage of capped RNAs. J. Virol. 76, 8989–9001 (2002)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. González, S. & Ortin, J. Characterization of influenza virus PB1 protein binding to viral RNA: two separate regions of the protein contribute to the interaction domain. J. Virol. 73, 631–637 (1999)

    Article  PubMed  PubMed Central  Google Scholar 

  45. Li, M. L., Ramirez, B. C. & Krug, R. M. 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, 5844–5852 (1998)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Jung, T. E. & Brownlee, G. G. A new promoter-binding site in the PB1 subunit of the influenza A virus polymerase. J. Gen. Virol. 87, 679–688 (2006)

    Article  CAS  PubMed  Google Scholar 

  47. Kerry, P. S., Willsher, N. & Fodor, E. A cluster of conserved basic amino acids near the C-terminus of the PB1 subunit of the influenza virus RNA polymerase is involved in the regulation of viral transcription. Virology 373, 202–210 (2008)

    Article  CAS  PubMed  Google Scholar 

  48. Leahy, M. B., Pritlove, D. C., Poon, L. L. & Brownlee, G. G. Mutagenic analysis of the 5′ arm of the influenza A virus virion RNA promoter defines the sequence requirements for endonuclease activity. J. Virol. 75, 134–142 (2001)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Rao, P., Yuan, W. & Krug, R. M. Crucial role of CA cleavage sites in the cap-snatching mechanism for initiating viral mRNA synthesis. EMBO J. 22, 1188–1198 (2003)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Poon, L. L., Pritlove, D. C., Sharps, J. & Brownlee, G. G. The RNA polymerase of influenza virus, bound to the 5′ end of virion RNA, acts in cis to polyadenylate mRNA. J. Virol. 72, 8214–8219 (1998)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Nie, Y., Bellon-Echeverria, I., Trowitzsch, S., Bieniossek, C. & Berger, I. Multiprotein complex production in insect cells by using polyproteins. Methods Mol. Biol. 1091, 131–141 (2014)

    Article  CAS  PubMed  Google Scholar 

  52. Kabsch, W. Integration, scaling, space-group assignment and post-refinement. Acta Crystallogr. D 66, 133–144 (2010)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Tefsen, B. et al. The N-terminal domain of PA from bat-derived influenza-like virus H17N10 has endonuclease activity. J. Virol. 88, 1935–1941 (2014)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  54. Murshudov, G. N. Refinement of macromolecular structures by the maximum-likelihood method. Acta Crystallogr. D 53, 240–255 (1997)

    Article  CAS  PubMed  Google Scholar 

  55. DeLano, W. L. The PyMOL Molecular Graphics System; http://www.pymol.sourceforge.net (Schrödinger, LLC, 2002)

  56. Chen, V. B. et al. MolProbity: all-atom structure validation for macromolecular crystallography. Acta Crystallogr. D. 66, 12–21 (2010)

    Article  CAS  PubMed  Google Scholar 

  57. De la Peña, M., Kyrieleis, O. J. & Cusack, S. Structural insights into the mechanism and evolution of the vaccinia virus mRNA cap N7 methyl-transferase. EMBO J. 26, 4913–4925 (2007)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Acknowledgements

We thank members of the ESRF-EMBL Joint Structural Biology Group for access to European Synchrotron Radiation Facility (ESRF) beamlines, staff of the European Molecular Biology Laboratory (EMBL) eukaryotic expression and high-throughput crystallization facilities within the Partnership for Structural Biology (PSB), D. Hart for help with construct design, and H. Malet for electron microscopy. This work was supported by ERC Advanced Grant V-RNA (322586) to S.C.

Author information

Author notes

  1. Alexander Pflug, Delphine Guilligay and Stefan Reich: These authors contributed equally to this work.

Authors and Affiliations

  1. European Molecular Biology Laboratory, Grenoble Outstation, 71 Avenue des Martyrs, CS 90181, 38042 Grenoble Cedex 9, France,

    Alexander Pflug, Delphine Guilligay, Stefan Reich & Stephen Cusack

  2. University Grenoble Alpes-Centre National de la Recherche Scientifique-EMBL Unit of Virus Host-Cell Interactions, 71 Avenue des Martyrs, CS 90181, 38042 Grenoble Cedex 9, France,

    Alexander Pflug, Delphine Guilligay, Stefan Reich & Stephen Cusack

Authors
  1. Alexander Pflug
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Delphine Guilligay
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Stefan Reich
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Stephen Cusack
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

A.P. did protein expression, purification and crystallization, with help from S.R. and D.G. who also did activity assays. A.P. did X-ray data collection and, together with S.C., did crystallographic analysis. S.C. supervised the project and wrote the paper with input from the other authors.

Corresponding author

Correspondence to Stephen Cusack.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Extended data figures and tables

Extended Data Figure 1 Production of influenza A polymerase heterotrimer.

a, The heterotrimeric bat polymerase was recombinantly expressed in insect cells as a self-cleaving polyprotein. N-terminally it encodes the tobacco etch virus (TEV) protease that cleaves C-terminal to the amino-acid sequence ENLYFQ (in italics), and releases N-terminally His-tagged PA, PB1, C-terminally strep-tagged PB2 and cyan fluorescent protein (CFP) for facilitated monitoring of expression. Arrows indicate the N-to-C-terminal direction and the termini of each mature protein. The histidine and streptavidin tags are underlined. b, After ammonium sulphate precipitation, immobilized metal ion affinity chromatography, engineered streptavidin (strep-tactin) affinity and heparin chromatography, the final purification step consisted of size-exclusion chromatography. The elution profile (monitored by the absorbance at 280 nm) with a single and nearly symmetric peak suggests a homogeneous and monomeric polymerase complex. mAU, milli-absorption unit. c, Fractions of the final size-exclusion chromatography were subjected to 10% SDS–PAGE followed by Coomassie blue staining. Lane 1 contains the molecular mass markers and lanes 2–7 the eluate with PA (85.4 kilodaltons (kDa)), PB1 (87.8 kDa) and PB2 (91.0 kDa). d, Recombinant bat FluA polymerase was visualized by electron microscopy following negative staining with sodium silico-tungstate of a 0.02 mg ml−1 protein sample. The image demonstrates that the sample is homogeneous and monodisperse with a V- or doughnut-like shape and central cavity.

Extended Data Figure 2 Endonuclease, RNA transcription and RNA replication activities of recombinant FluA polymerase.

a, Mini-panhandle vRNA: 5′-pppAGUAGUAACAAGAGGGUAUUGUAUACCUCUGCUUCUGCU-3′. b, Separate 5′ and 3′ ends: 5′: 5′-pAGUAGUAACAAGAGGGUA-3′; 3′: 5′-UAUACCUCUGCUUCUGCU-3′. c, Endonuclease, cap-dependent transcription and ApG-primed replication assays. Cleavage of the cap donor is visible in lanes 2–6. Capped transcripts are visible in lanes 10 (from vRNA panhandle template) and 13 (from separated 5′ and 3′ vRNA ends) as well as cRNA produced in lanes 17 and 20. Markers, with size shown on the left, are RNA ladders labelled with 32P-pCp nucleotide. d, e, Time course of unprimed (d) and ApG-primed (e) vRNA replication by bat influenza A polymerase. The products of replication (cRNA) are indicated with an arrow. Ladders (lanes L) are 32P-pCp nucleotide-labelled RNA oligomers. ApG-primed replication is more efficient than unprimed replication.

Extended Data Figure 3 Surface views of the FluA heterotrimer with bound vRNA promoter.

a–d, Four surface views at roughly 0° (a), 180° (b), 110° (c) and 290° (d) rotations with PA, PB1 and PB2 uniformly green, cyan and red, respectively. Major subdomains are labelled. The vRNA 5′ and 3′ ends are pink and yellow, respectively.

Extended Data Figure 4 PA and PB2 structure and new inter-subunit interactions.

a, Interactions of the PA-linker (green tube) with the outer surface of the fingers (pale cyan) and palm (pale salmon) domains of PB1. Contacts are mediated by both highly conserved hydrophobic residues (for example, PA residues Phe 205, Phe 211, Leu 214, Pro 220, Tyr 226, Phe 229, Tyr 232, Val 233, Ile 242, Leu 246, Met 249 and Val 253) and polar interactions (for example, PA Glu 203, Lys 230, Glu 243 and Lys 245 to PB1 Arg 162, Glu 331, His 465 and Asp 86, respectively). b, Transparent surface diagram showing the anchoring of the PA endonuclease domain (forest green) onto the PB1-Cter–PB2-Nter interface region (cyan/red) and its position relative to the PB2 cap-binding domain (orange). The nuclease helix α4 packs parallel to the penultimate PB1 helix α21 involving both hydrophobic (for example, PA Ile 86, Ile 90 and Ile 94 with PB1 Ser 720, Ile 724 and Ile 728, respectively) and polar interactions (for example, PA Glu 77 with PB1 Arg 727). Other contacts include the PB2 170-loop interacting with the same PA helix α4 in the vicinity of Trp 88. Also the endonuclease insertion (PA 70-loop, residues 67–74) packs on the first part of the last PB1 helix α22. The total buried surface area between the endonuclease and PB1/PB2 is 2,265 Å2.

Extended Data Figure 5 NTP and template tunnels in PB1.

a, View straight along the putative NTP entrance tunnel towards the putative priming loop (magenta) in the internal cavity. The NTP channel is lined with basic residues from the fingertips (Lys 235, Lys 237 and Arg 239, blue), fingers (Arg 45, cyan) and palm (Lys 308, Lys 480 and Lys 481, red) that are absolutely conserved in all influenza strains. The fingertips are in close proximity to PA helices α20 and α21 and to the loop of the 5′ hook. b, Surface view as in a showing that the putative priming loop in the interior cavity is visible through the NTP tunnel. c, View straight along the template entrance tunnel towards the priming loop (magenta) in the internal cavity. The tunnel is lined by residues conserved in all influenza strains and from all three subunits, Arg 507 and Asp 509 from PA (green), Tyr 30, Arg 126, Met 227, Lys 229 and Asp 230 from PB1 (cyan), and Arg 38, Lys 41 and Asn 42 from PB2 (red). d, Surface view as in c showing that the internal priming loop is visible through the template tunnel.

Extended Data Figure 6 Recognition of the vRNA 3′ end.

Protein interactions of the distal 3′ end showing the role of PB2-Nter (red). PB2 residues Arg 46 and Trp 49 and PA residue Lys 567 stabilize the sharp turn between 3′ nucleotides C8 and G9. PB2 Arg 38 and PB1-Cter residues Asn 671, Arg 672 and Asn 676 also bind the 3′ end. In the accompanying paper18, Fig. 2a shows the interactions with the complete 3′ end as observed in the FluB vRNA complex.

Extended Data Figure 7 vRNA arrangement in the bat polymerase crystals.

Simplified diagram showing vRNA sequence and secondary structure in the bat FluA crystals including vRNA-mediated crystal contact (inverted sequences) that forms an extended duplex. Crystals were grown with 3′-end nucleotides 1–18 or 3–18, but only those from 6–18 were visible (hence 1–5 are in italics).

Extended Data Table 1 Data collection and refinement statistics for bat FluA polymerase
Full size table
Extended Data Table 2 Direct polar polymerase–vRNA contacts for the bat FluA structure
Full size table

Supplementary information

Supplementary Information

This file contains Supplementary Figure 1, Supplementary Discussions and Supplementary References. (PDF 1975 kb)

360° rotation of bat FluA structure in ribbon representation about the vertical axis

View and colouring as in Fig. 1 (AVI 16280 kb)

360° rotation of bat FluA structure in surface representation about the vertical axis

View and colouring as in Fig. 1. (AVI 24293 kb)

PowerPoint slides

Rights and permissions

Reprints and Permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pflug, A., Guilligay, D., Reich, S. et al. Structure of influenza A polymerase bound to the viral RNA promoter. Nature 516, 355–360 (2014). https://doi.org/10.1038/nature14008

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nature14008

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing