RNA-dependent RNA polymerases from Flaviviridae
RNA-dependent RNA polymerases from Flaviviridae
复制标题
DOI：
10.1016/j.sbi.2009.10.015
复制
发表时间：
2009-12-01
影响因子：
6.8
通讯作者：
Rossmann, Michael G.
中科院分区：
文献类型：
--
作者：
Choi, Kyung H.;Rossmann, Michael G.
黄病毒科的病毒基因组复制是通过病毒编码的RNA依赖性RNA聚合酶（RdRp）进行的。这些病毒通过与小核糖核酸病毒科使用的引物依赖性机制不同的从头机制启动RNA合成。与所有聚合酶一样，黄病毒科RdRps的结构类似于具有特征性手指、手掌和拇指结构域的右手。区分黄病毒科RdRps与其他聚合酶的结构特征是大拇指结构域和包围活性位点的C-末端基序。这种结构域排列限制了模板结合通道的体积，仅允许单链RNA进入活性位点。虽然聚合酶的这种封闭形式对于稳定从头起始复合物是理想的，但预期显著的构象变化适应含有RNA双链体产物的延伸复合物。
Viral genome replication in Flaviviridae is carried out by a virally encoded RNA-dependent RNA polymerase (RdRp). These viruses initiate the RNA synthesis via a de novo mechanism that differs from the primer-dependent mechanism used by Picornaviridae. Like all polymerases, the structure of Flaviviridae RdRps resembles a right hand with characteristic fingers, palm, and thumb domains. Structural features that distinguish Flaviviridae RdRps from other polymerases are a large thumb domain and a C-terminal motif that encircles the active site. This domain arrangement restricts the volume of the template-binding channel, allowing only single-stranded RNA to enter the active site. While this closed form of the polymerase is ideal to stabilize a de novo initiation complex, significant conformational changes are expected to accommodate the elongation complex containing the RNA duplex product.