Structural basis of viral RNA-dependent RNA polymerase catalysis and translocation
Structural basis of viral RNA-dependent RNA polymerase catalysis and translocation
复制标题
病毒RNA依赖性RNA聚合酶催化和易位的结构基础
DOI：
10.1073/pnas.1602591113
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发表时间：
2016-07-12
影响因子：
11.1
通讯作者：
Gong, Peng
中科院分区：
文献类型：
--
作者：
Shu, Bo;Gong, Peng
病毒RNA依赖性RNA聚合酶（RdRPs）在病毒基因组复制和转录中起重要作用。我们以前报道了脊髓灰质炎病毒RdRP核苷酸添加循环（NAC）的几种结构状态，揭示了一个独特的棕榈结构域为基础的活性位点关闭机制，并提出了一个六态NAC模型，包括一个假设的状态代表易位中间体。使用RdRP从另一个人的肠道病毒，肠道病毒71，在这里，我们报告七个RdRP延伸复杂的结构来自晶格，允许三个NAC事件。这些结构表明，在初始NTP结合和NTP诱导的活性位点关闭事件的关键顺序，并揭示了一个真正的易位中间体具有不对称运动的模板-产物双链体。我们的工作提供了理解病毒RdRPs中NTP识别和易位机制的重要缺失环节，并强调了病毒RdRPs与其他进行性聚合酶相比的独特性。
Viral RNA-dependent RNA polymerases (RdRPs) play essential roles in viral genome replication and transcription. We previously reported several structural states of the poliovirus RdRP nucleotide addition cycle (NAC) that revealed a unique palm domain-based active site closure mechanism and proposed a six-state NAC model including a hypothetical state representing translocation intermediates. Using the RdRP from another human enterovirus, enterovirus 71, here we report seven RdRP elongation complex structures derived from a crystal lattice that allows three NAC events. These structures suggested a key order of events in initial NTP binding and NTP-induced active site closure and revealed a bona fide translocation intermediate featuring asymmetric movement of the template-product duplex. Our work provides essential missing links in understanding NTP recognition and translocation mechanisms in viral RdRPs and emphasizes the uniqueness of the viral RdRPs compared with other processive polymerases.