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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 / PubMed Central
MethodsEM (helical sym.) / EM (single particle) / EM (subtomogram averaging)
Resolution5.1 - 32.0 Å
Structure data

EMDB-44980, PDB-9c4h:
Double helical structure of influenza D RNP complex
Method: EM (helical sym.) / Resolution: 8.6 Å

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

EMDB-44982: Loop end of influenza D virus RNP, class 1
Method: EM (single particle) / Resolution: 10.3 Å

EMDB-44983: Structure of the loop end of influenza D virus RNP complex, class 2
Method: EM (single particle) / Resolution: 9.5 Å

EMDB-44984: Structure of influenza A RNP, 4xNP local reconstruction, class 1
Method: EM (subtomogram averaging) / Resolution: 9.7 Å

EMDB-44986: Structure of influenza A RNP, 4xNP local reconstruction, class 2
Method: EM (subtomogram averaging) / Resolution: 9.7 Å

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

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

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

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

EMDB-44994: NP subunits next to the polymerase at the end of influenza D virus RNP, piece 1
Method: EM (subtomogram averaging) / Resolution: 19.0 Å

EMDB-44996: The influenza D virus polymerase at the end of RNP complex
Method: EM (subtomogram averaging) / Resolution: 20.3 Å

EMDB-44997: The nucleoprotein subunits next the polymerase in the middle of influenza D RNP, piece 1
Method: EM (subtomogram averaging) / Resolution: 17.0 Å

EMDB-44998: The influenza D virus polymerase in the middle of RNP complex
Method: EM (subtomogram averaging) / Resolution: 17.0 Å

EMDB-45187: Subtomogram averaging of the polymerase end of influenza RNP complex
Method: EM (subtomogram averaging) / Resolution: 32.0 Å

EMDB-45188: Subtomogram averaging of influenza D virus RNP during elongation
Method: EM (subtomogram averaging) / Resolution: 29.0 Å

EMDB-48532: NP subunits next to the polymerase at the end of influenza D virus RNP, piece 2
Method: EM (subtomogram averaging) / Resolution: 19.0 Å

EMDB-48533: The nucleoprotein subunits next the polymerase in the middle of influenza D RNP, piece 2
Method: EM (subtomogram averaging) / Resolution: 19.0 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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