Crystal Structure of a Nucleocapsid-Like Nucleoprotein-RNA Complex of Respiratory Syncytial Virus

The respiratory syncytial virus (RSV) is an important human pathogen, yet neither a vaccine nor effective therapies are available to treat infection. To help elucidate the replication mechanism of this RNA virus, we determined the three-dimensional (3D) crystal structure at 3.3 Å resolution of a dec...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2009-11, Vol.326 (5957), p.1279-1283
Main Authors: Tawar, Rajiv G, Duquerroy, Stéphane, Vonrhein, Clemens, Varela, Paloma F, Damier-Piolle, Laurence, Castagné, Nathalie, MacLellan, Kirsty, Bedouelle, Hugues, Bricogne, Gérard, Bhella, David, Eléouët, Jean-François, Rey, Félix A
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Binding Sites
Biological and medical sciences
Cryoelectron Microscopy
Crystal structure
Crystallography, X-Ray
Fundamental and applied biological sciences. Psychology
Human respiratory syncytial virus
Image Processing, Computer-Assisted
Life Sciences
Microbiology
Models, Molecular
Molecular Sequence Data
Morphology, structure, chemical composition, physicochemical properties
Nucleic Acid Conformation
Nucleocapsid
Nucleocapsid Proteins
Nucleocapsid Proteins - chemistry
Nucleocapsid Proteins - metabolism
Nucleotides
Phosphates
Protein Structure, Secondary
Protein Structure, Tertiary
Protein Subunits
Protein Subunits - chemistry
Protein Subunits - metabolism
Respiratory syncytial virus
Respiratory Syncytial Viruses
Respiratory Syncytial Viruses - chemistry
Respiratory Syncytial Viruses - metabolism
Rhabdoviridae
Ribonucleic acid
RNA
RNA, Viral
RNA, Viral - chemistry
RNA, Viral - metabolism
Viral morphology
Virology
Viruses
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Summary:The respiratory syncytial virus (RSV) is an important human pathogen, yet neither a vaccine nor effective therapies are available to treat infection. To help elucidate the replication mechanism of this RNA virus, we determined the three-dimensional (3D) crystal structure at 3.3 Å resolution of a decameric, annular ribonucleoprotein complex of the RSV nucleoprotein (N) bound to RNA. This complex mimics one turn of the viral helical nucleocapsid complex, which serves as template for viral RNA synthesis. The RNA wraps around the protein ring, with seven nucleotides contacting each N subunit, alternating rows of four and three stacked bases that are exposed and buried within a protein groove, respectively. Combined with electron microscopy data, this structure provides a detailed model for the RSV nucleocapsid, in which the bases are accessible for readout by the viral polymerase. Furthermore, the nucleoprotein structure highlights possible key sites for drug targeting.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.1177634