Structural characterization of recombinant IAV polymerase reveals a stable complex between viral PA-PB1 heterodimer and host RanBP5.

Abstract : The genome of influenza A virus (IAV) comprises eight RNA segments (vRNA) which are transcribed and replicated by the heterotrimeric IAV RNA-dependent RNA-polymerase (RdRp). RdRp consists of three subunits (PA, PB1 and PB2) and binds both the highly conserved 3'- and 5'-ends of the vRNA segment. The IAV RdRp is an important antiviral target, but its structural mechanism has remained largely elusive to date. By applying a polyprotein strategy, we produced RdRp complexes and define a minimal human IAV RdRp core complex. We show that PA-PB1 forms a stable heterodimeric submodule that can strongly interact with 5'-vRNA. In contrast, 3'-vRNA recognition critically depends on the PB2 N-terminal domain. Moreover, we demonstrate that PA-PB1 forms a stable and stoichiometric complex with host nuclear import factor RanBP5 that can be modelled using SAXS and we show that the PA-PB1-RanPB5 complex is no longer capable of 5'-vRNA binding. Our results provide further evidence for a step-wise assembly of IAV structural components, regulated by nuclear transport mechanisms and host factor binding.
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Article dans une revue
Scientific Reports, Nature Publishing Group, 2016, 6, pp.24727. 〈10.1038/srep24727〉
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http://hal.univ-grenoble-alpes.fr/hal-01342969
Contributeur : Frank Thomas <>
Soumis le : jeudi 7 juillet 2016 - 11:25:54
Dernière modification le : jeudi 11 janvier 2018 - 06:15:24

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Christopher Swale, Alexandre Monod, Laura Tengo, Alice Labaronne, Frédéric Garzoni, et al.. Structural characterization of recombinant IAV polymerase reveals a stable complex between viral PA-PB1 heterodimer and host RanBP5.. Scientific Reports, Nature Publishing Group, 2016, 6, pp.24727. 〈10.1038/srep24727〉. 〈hal-01342969〉

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