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Nat Struct Mol Biol. 2014 Sep;21(9):754-9. doi: 10.1038/nsmb.2868. Epub 2014 Aug 10.

Structure of Nipah virus unassembled nucleoprotein in complex with its viral chaperone.

Author information

1
1] Université Grenoble Alpes, Unit of Virus Host Cell Interactions, Grenoble, France. [2] CNRS, Unit of Virus Host Cell Interactions, Grenoble, France.
2
International Centre for Research in Infectiology (CIRI), INSERM U1111-CNRS UMR5308, Université Lyon 1, Ecole Normale Supérieure de Lyon, Lyon, France.
3
1] Université Grenoble Alpes, Institut de Biologie Structurale, Grenoble, France. [2] CNRS, Institut de Biologie Structurale, Grenoble, France. [3] Commissariat à l'Énergie Atomique (CEA), Institut de Biologie Structurale, Grenoble, France.

Abstract

Nipah virus (NiV) is a highly pathogenic emergent paramyxovirus causing deadly encephalitis in humans. Its replication requires a constant supply of unassembled nucleoprotein (N(0)) in complex with its viral chaperone, the phosphoprotein (P). To elucidate the chaperone function of P, we reconstituted NiV the N(0)-P core complex and determined its crystal structure. The binding of the N-terminal region of P blocks the polymerization of N by interfering with subdomain exchange between N protomers and keeps N(0) in an open conformation, ready to grasp an RNA molecule. We found that a peptide derived from the N-binding region of P protects cells against viral infection and demonstrated by structure-based mutagenesis that this peptide acts by inhibiting N(0)-P formation. These results provide new insights about the assembly of N along genomic RNA and validate the N(0)-P complex as a target for drug development.

PMID:
25108352
DOI:
10.1038/nsmb.2868
[Indexed for MEDLINE]

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