title: Structure of the paramyxovirus parainfluenza virus 5 nucleoprotein-RNA complex.
abstract: 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. 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. This rotation would expose the RNA for the viral polymerase activity without major disruption of the nucleocapsid structure.
authors.affiliation: Howard Hughes Medical Institute, Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208-3500.
authors.forename: Maher
authors.initials: M
authors.lastname: Alayyoubi
authors.affiliation: Howard Hughes Medical Institute, Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208-3500.
authors.forename: George P
authors.initials: GP
authors.lastname: Leser
authors.affiliation: Howard Hughes Medical Institute, Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208-3500.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Kors
authors.affiliation: Howard Hughes Medical Institute, Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208-3500 ralamb@northwestern.edu.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Lamb
mesh_terms: D001665:Binding Sites; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000821:virology; D008854:Microscopy, Electron; D008958:Models, Molecular; D009698:Nucleoproteins / Q000737:chemistry*; D045402:Parainfluenza Virus 5 / Q000737:chemistry*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012367:RNA, Viral / Q000737:chemistry*
chemical_list: D009698:Nucleoproteins; D012367:RNA, Viral
keywords: atomic structure; nucleocapsid ring; nucleoprotein; paramyxovirus; ribonucleoprotein
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