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TitleMolecular basis of influenza ribonucleoprotein complex assembly and processive RNA synthesis.
Journal, issue, pagesScience, Vol. 388, Issue 6748, Page eadq7597, Year 2025
Publish dateMay 15, 2025
AuthorsRuchao Peng / Xin Xu / Binod Nepal / Yikang Gong / Fenglin Li / Max B Ferretti / Mingyang Zhou / Kristen W Lynch / George M Burslem / Sandhya Kortagere / Ronen Marmorstein / Yi-Wei Chang /
PubMed AbstractInfluenza viruses replicate and transcribe their genome in the context of a conserved ribonucleoprotein (RNP) complex. By integrating cryo-electron microscopy single-particle analysis and cryo- ...Influenza viruses replicate and transcribe their genome in the context of a conserved ribonucleoprotein (RNP) complex. By integrating cryo-electron microscopy single-particle analysis and cryo-electron tomography, we define the influenza RNP as a right-handed, antiparallel double helix with the viral RNA encapsidated in the minor groove. Individual nucleoprotein subunits are connected by a flexible tail loop that inserts into a conserved pocket in its neighbor. We visualize the viral polymerase in RNP at different functional states, revealing how it accesses the RNA template while maintaining the double-helical architecture of RNP by strand sliding. Targeting the tail loop binding interface, we identify lead compounds as potential anti-influenza inhibitors. These findings elucidate the molecular determinants underpinning influenza virus replication and highlight a promising target for antiviral development.
External linksScience / PubMed:40373132
MethodsEM (single particle) / EM (subtomogram averaging) / EM (helical sym.)
Resolution5.1 - 9.2 Å
Structure data

44981

9bwv

EMDB-44981, PDB-9bwv:
Structure of influenza D RNP, 4xNP local resconstruction
Method: EM (single particle) / Resolution: 5.1 Å

44987

9bwz

EMDB-44987, PDB-9bwz:
Structure of influenza A RNP, 4xNP local reconstruction, class 3
Method: EM (subtomogram averaging) / Resolution: 9.2 Å

44989

9bx0

EMDB-44989, PDB-9bx0:
Structure of influenza A RNP, 4xNP local reconstruction, class 4
Method: EM (subtomogram averaging) / Resolution: 9.2 Å

44990

9bx1

EMDB-44990, PDB-9bx1:
Structure of influenza A RNP, 4xNP local reconstruction, class 5
Method: EM (subtomogram averaging) / Resolution: 8.0 Å

44993

9bx4

EMDB-44993, PDB-9bx4:
Structure of influenza A RNP, 4xNP local reconstruction, class 6
Method: EM (subtomogram averaging) / Resolution: 9.2 Å

PDB-9c4h:
Double helical structure of influenza D RNP complex
Method: ELECTRON MICROSCOPY / Resolution: 8.6 Å

Source
  • influenza d virus
  • influenza a virus
KeywordsVIRAL PROTEIN/RNA / Influenza / Ribonucleoprotein complex / nucleoprotein / VIRAL PROTEIN-RNA complex / VIRAL PROTEIN / RNA BINDING PROTEIN/RNA / RNA BINDING PROTEIN-RNA complex

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