Structural basis for encapsidation of genomic RNA by La Crosse Orthobunyavirus nucleoprotein

Proc Natl Acad Sci U S A. 2013 Apr 30;110(18):7246-51. doi: 10.1073/pnas.1302298110. Epub 2013 Apr 15.


The nucleoprotein (NP) of segmented negative-strand RNA viruses such as Orthomyxo-, Arena-, and Bunyaviruses coats the genomic viral RNA and together with the polymerase forms ribonucleoprotein particles (RNPs), which are both the template for replication and transcription and are packaged into new virions. Here we describe the crystal structure of La Crosse Orthobunyavirus NP both RNA free and a tetrameric form with single-stranded RNA bound. La Crosse Orthobunyavirus NP is a largely helical protein with a fold distinct from other bunyavirus genera NPs. It binds 11 RNA nucleotides in the positively charged groove between its two lobes, and hinged N- and C-terminal arms mediate oligomerization, allowing variable protein-protein interface geometry. Oligomerization and RNA binding are mediated by residues conserved in the Orthobunyavirus genus. In the twofold symmetric tetramer, 44 nucleotides bind in a closed ring with sharp bends at the NP-NP interfaces. The RNA is largely inaccessible within a continuous internal groove. Electron microscopy of RNPs released from virions shows them capable of forming a hierarchy of more or less compact irregular helical structures. We discuss how the planar, tetrameric NP-RNA structure might relate to a polar filament that upon supercoiling could be packaged into virions. This work gives insight into the RNA encapsidation and protection function of bunyavirus NP, but also highlights the need for dynamic rearrangements of the RNP to give the polymerase access to the template RNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Capsid / chemistry*
  • Genome, Viral / genetics*
  • La Crosse virus / chemistry*
  • La Crosse virus / genetics*
  • La Crosse virus / ultrastructure
  • Models, Molecular
  • Molecular Sequence Data
  • Nucleoproteins / chemistry*
  • Nucleoproteins / isolation & purification
  • Nucleoproteins / ultrastructure
  • Protein Structure, Secondary
  • RNA, Viral / chemistry*
  • RNA, Viral / genetics*
  • RNA, Viral / ultrastructure
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / isolation & purification
  • Sequence Alignment


  • Nucleoproteins
  • RNA, Viral
  • Recombinant Proteins

Associated data

  • PDB/4BGP
  • PDB/4BHH