Molecular basis of host-adaptation interactions between influenza virus polymerase PB2 subunit and ANP32A
| Autor: | Elise Delaforge, Damien Maurin, Sigrid Milles, Nicola Salvi, Martin Blackledge, Stephen Cusack, Darren J. Hart, Malene Ringkjøbing Jensen, Aldo Camacho Zarco, Sissy Kalayil |
|---|---|
| Přispěvatelé: | Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), European Molecular Biology Laboratory [Grenoble] (EMBL), HFSP fellowship LT001544/2017, ANR-10-INBS-0005,FRISBI,Infrastructure Française pour la Biologie Structurale Intégrée(2010), ANR-17-EURE-0003,CBH-EUR-GS,CBH-EUR-GS(2017), European Project: 796490 |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
[SDV]Life Sciences [q-bio] Mutant General Physics and Astronomy Virus Replication medicine.disease_cause 01 natural sciences MESH: Avian Proteins Heterotrimeric G protein MESH: Nuclear Magnetic Resonance Biomolecular Influenza A virus MESH: Animals lcsh:Science Polymerase 0303 health sciences Multidisciplinary [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry Molecular Biology/Structural Biology [q-bio.BM] biology Chemistry MESH: Influenza Human virus diseases Nuclear Proteins RNA-Binding Proteins 3. Good health Cell biology MESH: Birds MESH: Protein Domains Host adaptation MESH: RNA Replicase Protein Binding MESH: Mutation MESH: Influenza A Virus H5N1 Subtype Science Protein subunit 010402 general chemistry Intrinsically disordered proteins Article Virus General Biochemistry Genetics and Molecular Biology Avian Proteins Birds Viral Proteins 03 medical and health sciences Protein Domains Species Specificity MESH: Influenza in Birds Influenza Human medicine Animals Humans MESH: Protein Binding MESH: Species Specificity Binding site Nuclear Magnetic Resonance Biomolecular 030304 developmental biology MESH: Humans Influenza A Virus H5N1 Subtype MESH: Virus Replication General Chemistry RNA-Dependent RNA Polymerase MESH: Viral Proteins Influenza A virus subtype H5N1 0104 chemical sciences MESH: RNA-Binding Proteins 030104 developmental biology Influenza in Birds Mutation biology.protein lcsh:Q Influenza virus Solution-state NMR MESH: Nuclear Proteins |
| Zdroj: | Nature Communications Nature Communications, Nature Publishing Group, 2020, 11 (1), ⟨10.1038/s41467-020-17407-x⟩ Nature Communications, Nature Publishing Group, 2020, 11 (1), pp.3656. ⟨10.1038/s41467-020-17407-x⟩ Nature Communications, Vol 11, Iss 1, Pp 1-12 (2020) Nature Communications, 2020, 11 (1), pp.3656. ⟨10.1038/s41467-020-17407-x⟩ |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-020-17407-x⟩ |
| Popis: | 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. Avian influenza polymerase undergoes host adaptation in order to efficiently replicate in human cells. Here, the authors use NMR spectroscopy and quantitative ensemble modelling to describe the highly dynamic assemblies formed by the human-adapted or avian-adapted C-terminal domains with the respective ANP32A host proteins. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|