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TitleStructures of H5N1 influenza polymerase with ANP32B reveal mechanisms of genome replication and host adaptation.
Journal, issue, pagesNat Commun, Vol. 15, Issue 1, Page 4123, Year 2024
Publish dateMay 15, 2024
AuthorsEcco Staller / Loïc Carrique / Olivia C Swann / Haitian Fan / Jeremy R Keown / Carol M Sheppard / Wendy S Barclay / Jonathan M Grimes / Ervin Fodor /
PubMed AbstractAvian influenza A viruses (IAVs) pose a public health threat, as they are capable of triggering pandemics by crossing species barriers. Replication of avian IAVs in mammalian cells is hindered by ...Avian influenza A viruses (IAVs) pose a public health threat, as they are capable of triggering pandemics by crossing species barriers. Replication of avian IAVs in mammalian cells is hindered by species-specific variation in acidic nuclear phosphoprotein 32 (ANP32) proteins, which are essential for viral RNA genome replication. Adaptive mutations enable the IAV RNA polymerase (FluPolA) to surmount this barrier. Here, we present cryo-electron microscopy structures of monomeric and dimeric avian H5N1 FluPolA with human ANP32B. ANP32B interacts with the PA subunit of FluPolA in the monomeric form, at the site used for its docking onto the C-terminal domain of host RNA polymerase II during viral transcription. ANP32B acts as a chaperone, guiding FluPolA towards a ribonucleoprotein-associated FluPolA to form an asymmetric dimer-the replication platform for the viral genome. These findings offer insights into the molecular mechanisms governing IAV genome replication, while enhancing our understanding of the molecular processes underpinning mammalian adaptations in avian-origin FluPolA.
External linksNat Commun / PubMed:38750014 / PubMed Central
MethodsEM (single particle)
Resolution3.1 - 3.3 Å
Structure data

EMDB-18818, PDB-8r1j:
Structure of avian H5N1 influenza A polymerase dimer in complex with human ANP32B.
Method: EM (single particle) / Resolution: 3.2 Å

EMDB-18819: Structure of avian H5N1 influenza A polymerase dimer in complex with human ANP32B (Consensus map)
Method: EM (single particle) / Resolution: 3.3 Å

EMDB-18820: Structure of avian H5N1 influenza A polymerase dimer in complex with human ANP32B (Encapsidase focused).
Method: EM (single particle) / Resolution: 3.2 Å

EMDB-18821: Structure of avian H5N1 influenza A polymerase dimer in complex with human ANP32B (Replicase focused).
Method: EM (single particle) / Resolution: 3.2 Å

EMDB-18822, PDB-8r1l:
Structure of avian H5N1 influenza A polymerase in complex with human ANP32B.
Method: EM (single particle) / Resolution: 3.1 Å

Source
  • influenza a virus
  • homo sapiens (human)
KeywordsVIRAL PROTEIN / Influenza virus / replication platform / H5N1 / influenza adaptive mutations / host adaptation / viral polymerase / cryo-EM / HPAI.

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