Structure of the paramyxovirus parainfluenza virus 5 nucleoprotein in complex with an amino-terminal peptide of the phosphoprotein

Megha Aggarwal, George P. Leser, Christopher A. Kors, Robert A. Lamb*

*Corresponding author for this work

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Parainfluenza virus 5 (PIV5) belongs to the family Paramyxoviridae, which consists of enveloped viruses with a nonsegmented negative-strand RNA genome encapsidated by the nucleoprotein (N). Paramyxovirus replication is regulated by the phosphoprotein (P) through protein-protein interactions with N and the RNA polymerase (L). The chaperone activity of P is essential to maintain the unassembled RNA-free form of N in order to prevent nonspecific RNA binding and premature N oligomerization. Here, we determined the crystal structure of unassembled PIV5 N in complex with a P peptide (N0P) derived from the N terminus of P (P50) at 2.65 Å. The PIV5 N0P consists of two domains: an N-terminal domain (NTD) and a C-terminal domain (CTD) separated by a hinge region. The cleft at the hinge region of RNAbound PIV5 N was previously shown to be an RNA binding site. The N0P structure shows that the P peptide binds to the CTD of N and extends toward the RNA binding site to inhibit N oligomerization and, hence, RNA binding. Binding of P peptide also keeps the PIV5 N in the open form. A molecular dynamics (MD) analysis of both the open and closed forms of N shows the flexibility of the CTD and the preference of the N protein to be in an open conformation. The gradual opening of the hinge region, to release the RNA, was also observed. Together, these results advance our knowledge of the conformational swapping of N required for the highly regulated paramyxovirus replication.

Original languageEnglish (US)
Article numbere01304-17
JournalJournal of virology
Volume92
Issue number5
DOIs
StatePublished - Mar 1 2018

Keywords

  • Conformational change
  • Crystal structure
  • Nucleoprotein
  • PIV5
  • Paramyxovirus
  • Phosphoprotein
  • Replication

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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