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Title: Structure of the paramyxovirus parainfluenza virus 5 nucleoprotein–RNA complex

Journal Article · · Proceedings of the National Academy of Sciences of the United States of America
 [1];  [1];  [1];  [1]
  1. Northwestern Univ., Evanston, IL (United States). Dept. of Molecular Biosciences. Howard Hughes Medical Inst.

Parainfluenza virus 5 (PIV5) is a member of the Paramyxoviridae family of membrane-enveloped viruses with a negative-sense RNA genome that is packaged and protected by long filamentous nucleocapsid-helix structures (RNPs). These RNPs, consisting of ~2,600 protomers of nucleocapsid (N) protein, form the template for viral transcription and replication. In this paper, we have determined the 3D X-ray crystal structure of the nucleoprotein (N)-RNA complex from PIV5 to 3.11-Å resolution. The structure reveals a 13-mer nucleocapsid ring whose diameter, cavity, and pitch/height dimensions agree with EM data from early studies on the Paramyxovirinae subfamily of native RNPs, indicating that it closely represents one-turn in the building block of the RNP helices. The PIV5-N nucleocapsid ring encapsidates a nuclease resistant 78-nt RNA strand in its positively charged groove formed between the N-terminal (NTD) and C-terminal (CTD) domains of its successive N protomers. Six nucleotides precisely are associated with each N protomer, with alternating three-base-in three-base-out conformation. The binding of six nucleotides per protomer is consistent with the “rule of six” that governs the genome packaging of the Paramyxovirinae subfamily of viruses. PIV5-N protomer subdomains are very similar in structure to the previously solved Nipah-N structure, but with a difference in the angle between NTD/CTD at the RNA hinge region. Based on the Nipah-N structure we modeled a PIV5-N open conformation in which the CTD rotates away from the RNA strand into the inner spacious nucleocapsid-ring cavity. Finally, this rotation would expose the RNA for the viral polymerase activity without major disruption of the nucleocapsid structure.

Research Organization:
Northwestern Univ., Evanston, IL (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES); Michigan Economic Development Corporation (United States); Michigan Technology Tri-Corridor (United States)
Grant/Contract Number:
AC02-06CH11357; 085PI000817
OSTI ID:
1182328
Journal Information:
Proceedings of the National Academy of Sciences of the United States of America, Vol. 112, Issue 14; ISSN 0027-8424
Publisher:
National Academy of Sciences, Washington, DC (United States)Copyright Statement
Country of Publication:
United States
Language:
ENGLISH
Citation Metrics:
Cited by: 77 works
Citation information provided by
Web of Science

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