Crystal Structure of a Nucleocapsid-Like Nucleoprotein-RNA Complex of Respiratory Syncytial Virus
Crystal Structure of a Nucleocapsid-Like Nucleoprotein-RNA Complex of Respiratory Syncytial Virus
复制标题
DOI：
10.1126/science.1177634
复制
发表时间：
2009-11-27
期刊：
影响因子：
56.9
通讯作者：
Rey, Felix A.
中科院分区：
文献类型：
--
作者：
Tawar, Rajiv G.;Duquerroy, Stephane;Rey, Felix A.
呼吸道合胞病毒（RSV）是一种重要的人类病原体，但既没有疫苗也没有有效的治疗方法来治疗感染。为了帮助阐明这种RNA病毒的复制机制，我们在3.3埃分辨率下测定了RSV核蛋白（N）与RNA结合的十聚体环状核糖核蛋白复合物的三维（3D）晶体结构。该复合物模拟病毒螺旋核衣壳复合物的一个转角，其用作病毒RNA合成的模板。RNA包裹在蛋白质环周围，每个N亚基有七个核苷酸接触，交替排列的四个和三个堆叠的碱基分别暴露和埋在蛋白质沟内。结合电子显微镜的数据，这种结构提供了一个详细的模型RSV核衣壳，其中的碱基是可访问的读出由病毒聚合酶。此外，核蛋白结构突出了药物靶向的可能关键位点。
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 angstrom 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.