title: Structure of Nipah virus unassembled nucleoprotein in complex with its viral chaperone.
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.
authors.affiliation: 1] Université Grenoble Alpes, Unit of Virus Host Cell Interactions, Grenoble, France. [2] CNRS, Unit of Virus Host Cell Interactions, Grenoble, France.
authors.forename: Filip
authors.initials: F
authors.lastname: Yabukarski
authors.affiliation: International Centre for Research in Infectiology (CIRI), INSERM U1111-CNRS UMR5308, Université Lyon 1, Ecole Normale Supérieure de Lyon, Lyon, France.
authors.forename: Philip
authors.initials: P
authors.lastname: Lawrence
authors.affiliation: 1] Université Grenoble Alpes, Unit of Virus Host Cell Interactions, Grenoble, France. [2] CNRS, Unit of Virus Host Cell Interactions, Grenoble, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Tarbouriech
authors.affiliation: 1] Université Grenoble Alpes, Unit of Virus Host Cell Interactions, Grenoble, France. [2] CNRS, Unit of Virus Host Cell Interactions, Grenoble, France.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Bourhis
authors.affiliation: 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.
authors.forename: Elise
authors.initials: E
authors.lastname: Delaforge
authors.affiliation: 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.
authors.forename: Malene Ringkjøbing
authors.initials: MR
authors.lastname: Jensen
authors.affiliation: 1] Université Grenoble Alpes, Unit of Virus Host Cell Interactions, Grenoble, France. [2] CNRS, Unit of Virus Host Cell Interactions, Grenoble, France.
authors.forename: Rob W H
authors.initials: RW
authors.lastname: Ruigrok
authors.affiliation: 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.
authors.forename: Martin
authors.initials: M
authors.lastname: Blackledge
authors.affiliation: International Centre for Research in Infectiology (CIRI), INSERM U1111-CNRS UMR5308, Université Lyon 1, Ecole Normale Supérieure de Lyon, Lyon, France.
authors.forename: Viktor
authors.initials: V
authors.lastname: Volchkov
authors.affiliation: 1] Université Grenoble Alpes, Unit of Virus Host Cell Interactions, Grenoble, France. [2] CNRS, Unit of Virus Host Cell Interactions, Grenoble, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Jamin
mesh_terms: D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D057809:HEK293 Cells; D045464:Henipavirus Infections / Q000821:virology*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D045405:Nipah Virus / Q000737:chemistry / Q000502:physiology*; D009698:Nucleoproteins / Q000737:chemistry / Q000378:metabolism*; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D014764:Viral Proteins / Q000737:chemistry / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D009698:Nucleoproteins; D010750:Phosphoproteins; D014764:Viral Proteins
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