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Nucleocapsid protein structures from orthobunyaviruses reveal insight into ribonucleoprotein architecture and RNA polymerization

DOI: 10.1093/nar/gkt268 DOI Help
PMID: 23595147 PMID Help

Authors: Antonio Ariza (University of Leeds) , Sian Tanner (University of Leeds) , Cheryl T. Walter (University of Leeds) , Kyle C. Dent (University of Leeds) , Dale A. Shepherd (University of Leeds) , Weining Wu (University of Leeds) , Susan V. Matthews (University of Leeds) , Julian A. Hiscox (University of Liverpool) , Todd J. Green (University of Alabama at Birmingham) , Ming Luo (University of Alabama at Birmingham) , Richard M. Elliott , Anthony R. Fooks (Animal Health and Veterinary Laboratories Agency; The National Centre for Zoonosis Research, University of Liverpool) , Alison E. Ashcroft (University of Leeds) , Nicola J. Stonehouse (University of Leeds) , Neil A. Ranson (University of Leeds) , John N. Barr (University of Leeds) , Thomas A. Edwards (University of Leeds)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nucleic Acids Research

State: Published (Approved)
Published: April 2013

Open Access Open Access

Abstract: All orthobunyaviruses possess three genome segments of single-stranded negative sense RNA that are encapsidated with the virus-encoded nucleocapsid (N) protein to form a ribonucleoprotein (RNP) complex, which is uncharacterized at high resolution. We report the crystal structure of both the Bunyamwera virus (BUNV) N–RNA complex and the unbound Schmallenberg virus (SBV) N protein, at resolutions of 3.20 and 2.75 Å, respectively. Both N proteins crystallized as ring-like tetramers and exhibit a high degree of structural similarity despite classification into different orthobunyavirus serogroups. The structures represent a new RNA-binding protein fold. BUNV N possesses a positively charged groove into which RNA is deeply sequestered, with the bases facing away from the solvent. This location is highly inaccessible, implying that RNA polymerization and other critical base pairing events in the virus life cycle require RNP disassembly. Mutational analysis of N protein supports a correlation between structure and function. Comparison between these crystal structures and electron microscopy images of both soluble tetramers and authentic RNPs suggests the N protein does not bind RNA as a repeating monomer; thus, it represents a newly described architecture for bunyavirus RNP assembly, with implications for many other segmented negative-strand RNA viruses.

Journal Keywords: Models; Molecular; Nucleocapsid; Orthobunyavirus; Protein; RNA; Ribonucleoproteins; Transcription; Genetic; Virus Replication

Subject Areas: Biology and Bio-materials

Instruments: I04-1-Macromolecular Crystallography (fixed wavelength) , I04-Macromolecular Crystallography , I24-Microfocus Macromolecular Crystallography

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