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

• Published in: Science (American Association for the Advancement of Science) Vol. 326; no. 5957; pp. 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: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 27.11.2009; The American Association for the Advancement of Science; American Association for the Advancement of Science (AAAS)
• 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; Virus; Human respiratory syncytial virus; Mononegavirales; Pneumovirinae; RNA; Three dimensional structure; Nucleocapsid; Nucleoprotein; Molecular complex; Pneumovirus; Paramyxoviridae; Amino Acid Sequence; Protein Subunits; Secondary; Tertiary; Viral; Molecular Sequence Data; Protein Structure; Molecular; Crystallography; Computer-Assisted; Nucleocapsid Proteins; Cryoelectron Microscopy; Respiratory Syncytial Viruses; Image Processing; X-Ray; Models; Nucleic Acid Conformation; Binding Sites
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1177634

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.