Molecular basis of host-adaptation interactions between influenza virus polymerase PB2 subunit and ANP32A.
Animals
Avian Proteins
/ metabolism
Birds
/ virology
Humans
Influenza A Virus, H5N1 Subtype
/ genetics
Influenza in Birds
/ virology
Influenza, Human
/ virology
Mutation
Nuclear Magnetic Resonance, Biomolecular
Nuclear Proteins
/ metabolism
Protein Binding
/ genetics
Protein Domains
/ genetics
RNA-Binding Proteins
/ metabolism
RNA-Dependent RNA Polymerase
/ genetics
Species Specificity
Viral Proteins
/ genetics
Virus Replication
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
21 07 2020
21 07 2020
Historique:
received:
13
03
2020
accepted:
29
06
2020
entrez:
23
7
2020
pubmed:
23
7
2020
medline:
10
9
2020
Statut:
epublish
Résumé
Avian influenza polymerase undergoes host adaptation in order to efficiently replicate in human cells. Adaptive mutants are localised on the C-terminal (627-NLS) domains of the PB2 subunit. In particular, mutation of PB2 residue 627 from E to K rescues polymerase activity in mammalian cells. A host transcription regulator ANP32A, comprising a long C-terminal intrinsically disordered domain (IDD), is responsible for this adaptation. Human ANP32A IDD lacks a 33 residue insertion compared to avian ANP32A, and this deletion restricts avian influenza polymerase activity. We used NMR to determine conformational ensembles of E627 and K627 forms of 627-NLS of PB2 in complex with avian and human ANP32A. Human ANP32A IDD transiently binds to the 627 domain, exploiting multivalency to maximise affinity. E627 interrupts the polyvalency of the interaction, an effect compensated by an avian-unique motif in the IDD. The observed binding mode is maintained in the context of heterotrimeric influenza polymerase, placing ANP32A in the immediate vicinity of known host-adaptive PB2 mutants.
Identifiants
pubmed: 32694517
doi: 10.1038/s41467-020-17407-x
pii: 10.1038/s41467-020-17407-x
pmc: PMC7374565
doi:
Substances chimiques
ANP32A protein, human
0
Avian Proteins
0
Nuclear Proteins
0
PB2 protein, Influenzavirus A
0
RNA-Binding Proteins
0
Viral Proteins
0
RNA-Dependent RNA Polymerase
EC 2.7.7.48
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3656Références
Lozano, R. et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 380, 2095–2128 (2012).
pubmed: 23245604
Nicholls, H. Pandemic Influenza: the Inside Story. PLoS Biol. 4, e50 (2006).
pubmed: 16464130
pmcid: 1363710
Almond, J. W. A single gene determines the host range of influenza virus. Nature 270, 617–618 (1977).
pubmed: 593388
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).
pubmed: 18769709
pmcid: 2515345
Mehle, A. & Doudna, J. A. Adaptive strategies of the influenza virus polymerase for replication in humans. Proc. Natl Acad. Sci. USA 106, 21312–21316 (2009).
pubmed: 19995968
Gabriel, G., Czudai-Matwich, V. & Klenk, H.-D. Adaptive mutations in the H5N1 polymerase complex. Virus Res. 178, 53–62 (2013).
pubmed: 23732876
Tarendeau, F. et al. Structure and nuclear import function of the C-terminal domain of influenza virus polymerase PB2 subunit. Nat. Struct. Mol. Biol. 14, 229–233 (2007).
pubmed: 17310249
Subbarao, E. K., Kawaoka, Y. & Murphy, B. R. Rescue of an influenza A virus wild-type PB2 gene and a mutant derivative bearing a site-specific temperature-sensitive and attenuating mutation. J. Virol. 67, 7223–7228 (1993).
pubmed: 8230444
pmcid: 238184
Massin, P., van der Werf, S. & Naffakh, N. Residue 627 of PB2 is a determinant of cold sensitivity in RNA replication of avian influenza viruses. J. Virol. 75, 5398–5404 (2001).
pubmed: 11333924
pmcid: 114948
de Jong, M. D. et al. Fatal outcome of human influenza A (H5N1) is associated with high viral load and hypercytokinemia. Nat. Med. 12, 1203–1207 (2006).
pubmed: 16964257
pmcid: 4333202
Kirui, J., Bucci, M. D., Poole, D. S. & Mehle, A. Conserved features of the PB2 627 domain impact influenza virus polymerase function and replication. J. Virol. 88, 5977–5986 (2014).
pubmed: 24623411
pmcid: 4093881
Reilly, P. T., Yu, Y., Hamiche, A. & Wang, L. Cracking the ANP32 whips: important functions, unequal requirement, and hints at disease implications. BioEssays N. Rev. Mol. Cell. Dev. Biol. 36, 1062–1071 (2014).
Long, J. S. et al. Species difference in ANP32A underlies influenza A virus polymerase host restriction. Nature 529, 101–104 (2016).
pubmed: 26738596
pmcid: 4710677
Sugiyama, K., Kawaguchi, A., Okuwaki, M. & Nagata, K. pp32 and APRIL are host cell-derived regulators of influenza virus RNA synthesis from cRNA. eLife 4, e08939 (2015).
pubmed: 26512887
pmcid: 4718810
Lowen, A. C. Virology: Host protein clips bird flu’s wings in mammals. Nature 529, 30–31 (2016).
pubmed: 26738587
Mehle, A. The avian influenza virus polymerase brings ANP32A home to roost. Cell Host Microbe 19, 137–138 (2016).
pubmed: 26867171
Domingues, P. & Hale, B. G. Functional insights into ANP32A-dependent influenza a virus polymerase host restriction. Cell Rep. 20, 2538–2546 (2017).
pubmed: 28903035
pmcid: 5608968
Baker, S. F., Ledwith, M. P. & Mehle, A. Differential splicing of ANP32A in birds alters its ability to stimulate RNA synthesis by restricted influenza polymerase. Cell Rep. 24, 2581–2588.e4 (2018).
pubmed: 30184493
pmcid: 6157632
Long, J. S., Mistry, B., Haslam, S. M. & Barclay, W. S. Host and viral determinants of influenza A virus species specificity. Nat. Rev. Microbiol. 17, 67 (2019).
pubmed: 30487536
Staller, E. et al. ANP32 proteins are essential for influenza virus replication in human cells. J. Virol. 93, e00217–e00219 (2019).
pubmed: 31217244
pmcid: 6694824
Zhang, H. et al. Fundamental contribution and host range determination of ANP32A and ANP32B in influenza A virus polymerase activity. J. Virol. 93, e00174–19 (2019).
pubmed: 30996088
pmcid: 6580979
Baker, S. F. & Mehle, A. ANP32B, or not to be, that is the question for influenza virus. eLife 8, e48084 (2019).
pubmed: 31179971
pmcid: 6557625
Long, J. S. et al. Species specific differences in use of ANP32 proteins by influenza A virus. eLife 8, e45066 (2019).
pubmed: 31159925
pmcid: 6548507
Mistry, B. et al. Elucidating the interactions between influenza virus polymerase and host factor ANP32A. J. Virol. 94, e01353–19 (2020).
pubmed: 31694956
pmcid: 7000967
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).
pubmed: 19144639
pmcid: 2652293
Pflug, A., Guilligay, D., Reich, S. & Cusack, S. Structure of influenza A polymerase bound to the viral RNA promoter. Nature 516, 355–360 (2014).
pubmed: 25409142
Delaforge, E. et al. Large-scale conformational dynamics control H5N1 influenza polymerase PB2 binding to importin α. J. Am. Chem. Soc. 137, 15122–15134 (2015).
pubmed: 26424125
Hengrung, N. et al. Crystal structure of the RNA-dependent RNA polymerase from influenza C virus. Nature 527, 114–117 (2015).
pubmed: 26503046
pmcid: 4783868
Thierry, E. et al. Influenza polymerase can adopt an alternative configuration involving a radical repacking of PB2 domains. Mol. Cell 61, 125–137 (2016).
pubmed: 26711008
pmcid: 4712189
Yamada, S. et al. Biological and structural characterization of a host-adapting amino acid in influenza virus. PLoS Pathog. 6, e1001034 (2010).
pubmed: 20700447
pmcid: 2916879
Salmon, L. et al. NMR characterization of long-range order in intrinsically disordered proteins. J. Am. Chem. Soc. 132, 8407–8418 (2010).
pubmed: 20499903
Reich, S. et al. Structural insight into cap-snatching and RNA synthesis by influenza polymerase. Nature 516, 361–366 (2014).
pubmed: 25409151
Soh, Y. S., Moncla, L. H., Eguia, R., Bedford, T. & Bloom, J. D. Comprehensive mapping of adaptation of the avian influenza polymerase protein PB2 to humans. eLife 8, e45079 (2019).
pubmed: 31038123
pmcid: 6491042
Wandzik, J. M., Kouba, T. & Cusack, S. Structure and function of influenza polymerase. Cold Spring Harb. Perspect. Med. a038372 (2020).
Fan, H. et al. Structures of influenza A virus RNA polymerase offer insight into viral genome replication. Nature 573, 287–290 (2019).
pubmed: 31485076
pmcid: 6795553
Jensen, M. R., Zweckstetter, M., Huang, J. & Blackledge, M. Exploring free-energy landscapes of intrinsically disordered proteins at atomic resolution using NMR spectroscopy. Chem. Rev. 114, 6632–6660 (2014).
pubmed: 24725176
Huang, J.-R. et al. Transient electrostatic interactions dominate the conformational equilibrium sampled by multidomain splicing factor U2AF65: a combined NMR and SAXS study. J. Am. Chem. Soc. 136, 7068–7076 (2014).
pubmed: 24734879
Milles, S. et al. Plasticity of an ultrafast interaction between nucleoporins and nuclear transport receptors. Cell 163, 734–745 (2015).
pubmed: 26456112
pmcid: 4622936
Borgia, A. et al. Extreme disorder in an ultrahigh-affinity protein complex. Nature 555, 61–66 (2018).
pubmed: 29466338
pmcid: 6264893
Hayashi, T., Wills, S., Bussey, K. A. & Takimoto, T. Identification of influenza A virus PB2 residues involved in enhanced polymerase activity and virus growth in mammalian cells at low temperatures. J. Virol. 89, 8042–8049 (2015).
pubmed: 26018156
pmcid: 4505657
Peng, Q. et al. Structural insight into RNA synthesis by influenza D polymerase. Nat. Microbiol. 4, 1750–1759 (2019).
pubmed: 31209309
Kouba, T., Drncová, P. & Cusack, S. Structural snapshots of actively transcribing influenza polymerase. Nat. Struct. Mol. Biol. 26, 460–470 (2019).
pubmed: 31160782
Fodor, E. & Te Velthuis, A. J. W. Structure and function of the influenza virus transcription and replication machinery. Cold Spring Harb. Perspect. Med. a038398 (2019).
Lukarska, M. et al. Structural basis of an essential interaction between influenza polymerase and Pol II CTD. Nature 541, 117–121 (2017).
pubmed: 28002402
Martin, I. S. et al. A mechanism for the activation of the influenza virus transcriptase. Mol. Cell 70, 1101–1110.e4 (2018).
Milles, S. et al. An ultraweak interaction in the intrinsically disordered replication machinery is essential for measles virus function. Sci. Adv. 4, eaat7778 (2018).
pubmed: 30140745
pmcid: 6105297
Büssow, K. et al. Structural genomics of human proteins–target selection and generation of a public catalogue of expression clones. Microb. Cell Factories 4, 21 (2005).
Braman, J., Papworth, C. & Greener, A. Site-directed mutagenesis using double-stranded plasmid DNA templates. Methods Mol. Biol. Clifton NJ 57, 31–44 (1996).
DELAGLIO, F. et al. NMRPipe - a multidimensional spectral processing system based on UNIX pipes. J. Biomol. NMR 6, 277–293 (1995).
pubmed: 8520220
Goddard, T. & Kneller, D. SPARKY 3. University of California, San Francisco.
Jung, Y.-S. & Zweckstetter, M. Mars - robust automatic backbone assignment of proteins. J. Biomol. NMR 30, 11–23 (2004).
pubmed: 15452431
de Chiara, C., Kelly, G., Frenkiel, T. A. & Pastore, A. NMR assignment of the leucine-rich repeat domain of LANP/Anp32a. J. Biomol. NMR 38, 177 (2007).
pubmed: 17180445
Fossat, M. J. et al. High-resolution mapping of a repeat protein folding free energy landscape. Biophys. J. 111, 2368–2376 (2016).
pubmed: 27926838
pmcid: 5153537
Marsh, J. A., Singh, V. K., Jia, Z. & Forman-Kay, J. D. Sensitivity of secondary structure propensities to sequence differences between alpha- and gamma-synuclein: implications for fibrillation. Protein Sci. Publ. Protein Soc. 15, 2795–2804 (2006).
Lakomek, N.-A., Ying, J. & Bax, A. Measurement of
pubmed: 22689066
pmcid: 3412688
Dominguez, C., Boelens, R. & Bonvin, A. M. J. J. HADDOCK: a protein-protein docking approach based on biochemical or biophysical information. J. Am. Chem. Soc. 125, 1731–1737 (2003).
pubmed: 12580598
Ozenne, V. et al. Flexible-meccano: a tool for the generation of explicit ensemble descriptions of intrinsically disordered proteins and their associated experimental observables. Bioinformatics 28, 1463–1470 (2012).
pubmed: 22613562
Kubáň, V. et al. Quantitative conformational analysis of functionally important electrostatic interactions in the intrinsically disordered region of delta subunit of bacterial RNA polymerase. J. Am. Chem. Soc. 141, 16817–16828 (2019).
pubmed: 31550880