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TitleCryo-EM structure of influenza polymerase bound to the cRNA promoter provides insights into the mechanism of viral replication.
Journal, issue, pagesCommun Biol, Vol. 9, Issue 1, Page 112, Year 2025
Publish dateDec 29, 2025
AuthorsYixi Wu / Minke Li / Huanhuan Li / Yifan Bai / Tianli Sun / Shaohui Huang / Yingfang Liu / Huanhuan Liang /
PubMed AbstractInfluenza virus polymerase (FluPol) synthesizes the complementary RNA (cRNA) and the viral RNA (vRNA) using distinct de novo initiation strategies during genome replication, known as internal and ...Influenza virus polymerase (FluPol) synthesizes the complementary RNA (cRNA) and the viral RNA (vRNA) using distinct de novo initiation strategies during genome replication, known as internal and terminal initiation, respectively. The de novo initiation mechanisms, especially the internal initiation process, which includes a template realignment process, are still not well understood. Here, we present a cryo-electron microscopy structure of H5N1 FluPol bound to the cRNA promoter. In combination with structural analyses and structure-guided mutagenesis studies, we identified several previously unreported structural features of FluPol essential for internal initiation. The B loop adopts an "open" conformation, allowing translocation of the 3' terminus of cRNA (3'-cRNA) template into the catalytic cavity. The dynamic of incoming 3'-cRNA template is limited by the priming and realignment loop (PR loop), which facilitates the cRNA template realignment process. An asparagine cluster above the catalytic cavity is required for polymerase activity. Our findings provide structural insights into the mechanism of replication internal initiation of FluPol.
External linksCommun Biol / PubMed:41461902 / PubMed Central
MethodsEM (single particle)
Resolution2.98 Å
Structure data

66772

9lck

EMDB-66772: Cryo-EM map of influenza polymerase bound to the cRNA promoter
PDB-9lck: Cryo-EM structure of influenza polymerase bound to cRNA promoter
Method: EM (single particle) / Resolution: 2.98 Å

Source
  • Insecta environmental sample (insect)
  • influenza a virus (strain a/goose/guangdong/1/1996 h5n1 genotype gs/gd)
KeywordsVIRAL PROTEIN/RNA / influenza polymerase / VIRAL PROTEIN-RNA complex

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