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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Crystallography, X-Ray
  • HEK293 Cells
  • Henipavirus Infections / virology*
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Nipah Virus / chemistry
  • Nipah Virus / physiology*
  • Nucleoproteins / chemistry
  • Nucleoproteins / metabolism*
  • Phosphoproteins / chemistry
  • Phosphoproteins / metabolism*
  • Protein Binding
  • Protein Conformation
  • Viral Proteins / chemistry
  • Viral Proteins / metabolism*
  • Virus Replication*


  • Nucleoproteins
  • Phosphoproteins
  • Viral Proteins

Associated data

  • PDB/4CO6