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
Institut Pasteur, Unité de Virologie Structurale, Département de Virologie and CNRS Unité de Recherche Associée (URA) 3015, 25 Rue du Dr Roux, 75724 Paris Cedex 15, France.
Science. 2009 Nov 27;326(5957):1279-83. 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 A 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.
呼吸道合胞病毒(RSV)是一种重要的人类病原体,但目前尚无疫苗或有效疗法可用于治疗该病毒感染。为了帮助阐明这种RNA病毒的复制机制,我们确定了呼吸道合胞病毒核蛋白(N)与RNA结合形成的十聚体环状核糖核蛋白复合物的三维(3D)晶体结构,分辨率为3.3埃。该复合物模拟了病毒螺旋核衣壳复合物的一圈,该复合物作为病毒RNA合成的模板。RNA环绕着蛋白质环,每个N亚基与七个核苷酸接触,分别有四排和三排交替堆叠的碱基,它们分别暴露在蛋白质凹槽内和埋在其中。结合电子显微镜数据,该结构为呼吸道合胞病毒核衣壳提供了一个详细模型,其中碱基可供病毒聚合酶读取。此外,核蛋白结构突出了可能的药物靶向关键位点。