RNA-Dependent RNA Polymerases of Picornaviruses: From the Structure to Regulatory Mechanisms.
RNA-Dependent RNA Polymerases of Picornaviruses: From the Structure to Regulatory Mechanisms.
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DOI：
10.3390/v7082829
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发表时间：
2015-08-06
期刊：
影响因子：
--
通讯作者：
Verdaguer N
中科院分区：
文献类型：
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作者：
Ferrer-Orta C;Ferrero D;Verdaguer N
RNA病毒通常编码其自身的RNA依赖性RNA聚合酶（RdRP）以确保基因组在受感染细胞内复制。RdRP功能不仅对病毒的生命周期至关重要，而且对其适应潜力也至关重要。低复制保真度和RdRP内缺乏校对和切除活性的组合导致高突变频率，使这些病毒能够快速适应不断变化的环境。本文综述了RdRP催化复合物的结构和功能方面的研究进展，主要集中在小核糖核酸病毒科。目前从这些病毒获得的结构数据提供了与RNA模板-引物结合、rNTP识别、催化和链易位相关的一系列构象状态的高分辨率快照。由于这些酶是开发抗病毒化合物的主要靶点，因此这些结构信息对于设计新疗法至关重要。
RNA viruses typically encode their own RNA-dependent RNA polymerase (RdRP) to ensure genome replication within the infected cells. RdRP function is critical not only for the virus life cycle but also for its adaptive potential. The combination of low fidelity of replication and the absence of proofreading and excision activities within the RdRPs result in high mutation frequencies that allow these viruses a rapid adaptation to changing environments. In this review, we summarize the current knowledge about structural and functional aspects on RdRP catalytic complexes, focused mainly in the Picornaviridae family. The structural data currently available from these viruses provided high-resolution snapshots for a range of conformational states associated to RNA template-primer binding, rNTP recognition, catalysis and chain translocation. As these enzymes are major targets for the development of antiviral compounds, such structural information is essential for the design of new therapies.