Contributors: European Molecular Biology Laboratory Grenoble (EMBL); Biologie des ARN et virus influenza - RNA Biology of Influenza Virus (CNRS-UMR3569); Institut Pasteur Paris (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité); 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); This work was partially funded by the ANR grant FluTranscript (ANR-18-CE18-0028), held jointly by S.C. and N.N. T.K. was funded by the ANR grants FluTranscript and ANR-10-LABX-62-IBEID. This work used the platforms at the Grenoble Instruct-ERIC Center (ISBG; UMS 3518 CNRS CEA-UGA-EMBL) with support from the French Infrastructure for Integrated Structural Biology (FRISBI; ANR-10-INSB-05-02) and GRAL, a project of the University Grenoble Alpes graduate school (Ecoles Universitaires de Recherche) CBH-EUR-GS (ANR-17-EURE-0003) within the Grenoble Partnership for Structural Biology. Open Access funding enabled and organized by Projekt DEAL.; ANR-18-CE11-0028,FluTranscript,Mécanisme moléculaire de transcription par la polymérase du virus de la grippe(2018); ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010); ANR-10-INBS-0005,FRISBI,Infrastructure Française pour la Biologie Structurale Intégrée(2010); ANR-17-EURE-0003,CBH-EUR-GS,CBH-EUR-GS(2017)
نبذة مختصرة : International audience ; Replication of influenza viral RNA depends on at least two viral polymerases, a parental replicase and an encapsidase, and cellular factor ANP32. ANP32 comprises an LRR domain and a long C-terminal low complexity acidic region (LCAR). Here we present evidence suggesting that ANP32 is recruited to the replication complex as an electrostatic chaperone that stabilises the encapsidase moiety within apo-polymerase symmetric dimers that are distinct for influenza A and B polymerases. The ANP32 bound encapsidase, then forms the asymmetric replication complex with the replicase, which is embedded in a parental ribonucleoprotein particle (RNP). Cryo-EM structures reveal the architecture of the influenza A and B replication complexes and the likely trajectory of the nascent RNA product into the encapsidase. The cryo-EM map of the FluB replication complex shows extra density attributable to the ANP32 LCAR wrapping around and stabilising the apo-encapsidase conformation. These structures give new insight into the various mutations that adapt avian strain polymerases to use the distinct ANP32 in mammalian cells.
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