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TitleAn intermediate state allows influenza polymerase to switch smoothly between transcription and replication cycles.
Journal, issue, pagesNat Struct Mol Biol, Vol. 30, Issue 8, Page 1183-1192, Year 2023
Publish dateJul 24, 2023
AuthorsHuanhuan Li / Yixi Wu / Minke Li / Lu Guo / Yaqi Gao / Quan Wang / Jihua Zhang / Zhaohua Lai / Xing Zhang / Lixin Zhu / Ping Lan / Zihe Rao / Yingfang Liu / Huanhuan Liang /
PubMed AbstractInfluenza polymerase (FluPol) transcribes viral mRNA at the beginning of the viral life cycle and initiates genome replication after viral protein synthesis. However, it remains poorly understood how ...Influenza polymerase (FluPol) transcribes viral mRNA at the beginning of the viral life cycle and initiates genome replication after viral protein synthesis. However, it remains poorly understood how FluPol switches between its transcription and replication states, especially given that the structural bases of these two functions are fundamentally different. Here we propose a mechanism by which FluPol achieves functional switching between these two states through a previously unstudied conformation, termed an 'intermediate state'. Using cryo-electron microscopy, we obtained a structure of the intermediate state of H5N1 FluPol at 3.7 Å, which is characterized by a blocked cap-binding domain and a contracted core region. Structural analysis results suggest that the intermediate state may allow FluPol to transition smoothly into either the transcription or replication state. Furthermore, we show that the formation of the intermediate state is required for both the transcription and replication activities of FluPol, leading us to conclude that the transcription and replication cycles of FluPol are regulated via this intermediate state.
External linksNat Struct Mol Biol / PubMed:37488357
MethodsEM (single particle)
Resolution3.6 - 3.7 Å
Structure data

EMDB-34496: The core region map of avian influenza A polymerase.
Method: EM (single particle) / Resolution: 3.6 Å

34497

8h69

EMDB-34497: The full-length map of avian influenza A polymerase.
PDB-8h69: Cryo-EM structure of influenza RNA polymerase
Method: EM (single particle) / Resolution: 3.7 Å

Source
  • Influenza A virus
  • Influenza (virus)
  • influenza a virus (a/goose/guangdong/1/1996(h5n1))
KeywordsVIRAL PROTEIN / RNA polymerase

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