Structures of influenza A and B replication complexes give insight into avian to human host adaptation and reveal a role of ANP32 as an electrostatic chaperone for the apo-polymerase.
Humans
Animals
Virus Replication
Molecular Chaperones
/ metabolism
Influenza A virus
/ metabolism
RNA-Binding Proteins
/ metabolism
Cryoelectron Microscopy
Static Electricity
Nuclear Proteins
/ metabolism
RNA, Viral
/ metabolism
Birds
/ virology
RNA-Dependent RNA Polymerase
/ metabolism
Influenza in Birds
/ virology
Models, Molecular
Influenza, Human
/ virology
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
19 Aug 2024
19 Aug 2024
Historique:
received:
08
02
2024
accepted:
16
07
2024
medline:
20
8
2024
pubmed:
20
8
2024
entrez:
19
8
2024
Statut:
epublish
Résumé
Replication of influenza viral RNA depends on at least two viral polymerases, a parental replicase and an encapsidase, and cellular factor ANP32. ANP32 comprises an LRR domain and a long C-terminal low complexity acidic region (LCAR). Here we present evidence suggesting that ANP32 is recruited to the replication complex as an electrostatic chaperone that stabilises the encapsidase moiety within apo-polymerase symmetric dimers that are distinct for influenza A and B polymerases. The ANP32 bound encapsidase, then forms the asymmetric replication complex with the replicase, which is embedded in a parental ribonucleoprotein particle (RNP). Cryo-EM structures reveal the architecture of the influenza A and B replication complexes and the likely trajectory of the nascent RNA product into the encapsidase. The cryo-EM map of the FluB replication complex shows extra density attributable to the ANP32 LCAR wrapping around and stabilising the apo-encapsidase conformation. These structures give new insight into the various mutations that adapt avian strain polymerases to use the distinct ANP32 in mammalian cells.
Identifiants
pubmed: 39160148
doi: 10.1038/s41467-024-51007-3
pii: 10.1038/s41467-024-51007-3
doi:
Substances chimiques
Molecular Chaperones
0
ANP32A protein, human
0
RNA-Binding Proteins
0
Nuclear Proteins
0
RNA, Viral
0
ANP32B protein, human
0
RNA-Dependent RNA Polymerase
EC 2.7.7.48
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
6910Subventions
Organisme : Agence Nationale de la Recherche (French National Research Agency)
ID : ANR-18-CE18-0028
Organisme : Agence Nationale de la Recherche (French National Research Agency)
ID : ANR-10-LABX-62-IBEID
Informations de copyright
© 2024. The Author(s).
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