Structural basis of viral RNA-dependent RNA polymerase nucleotide addition cycle in picornaviruses
Structural basis of viral RNA-dependent RNA polymerase nucleotide addition cycle in picornaviruses
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DOI：
10.1016/bs.enz.2021.06.002
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发表时间：
2021-01-01
期刊：
影响因子：
--
通讯作者：
Gong, Peng
中科院分区：
文献类型：
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作者：
Gong, Peng
RNA病毒编码的RNA依赖的RNA聚合酶(RdRPs)代表着一类独特的过程性核酸聚合酶，执行不依赖于DNA的复制/转录过程。尽管病毒RdRPs具有多种全球结构，但它们确实共享一个结构高度保守的活性部位，包括催化基序A-G。尽管有不同的启动模式，但RdRP伸长阶段的核苷酸加成循环(NAC)可能遵循一致的机制。在这一章中，我们使用小核糖核酸病毒RdRP延伸复合体的典型结构来说明RdRP NAC的作用机制。在NAC的化学前部分，RdRPs利用了一种独特的基于棕榈区的活性位点闭合，可以进一步分解为两个连续的步骤。在NAC的化学后部分，转位过程受到RdRP特异性基序G的严格控制，导致模板产物RNA的不对称运动。为了全面了解病毒Rdrp NAC，未来有必要阐明不匹配的NTPs或核苷酸类似物抗病毒药物的调节/干预机制。
RNA-dependent RNA polymerases (RdRPs) encoded by RNA viruses represent a unique class of processive nucleic acid polymerases, carrying out DNA-independent replication/transcription processes. Although viral RdRPs have versatile global structures, they do share a structurally highly conserved active site comprising catalytic motifs A-G. In spite of different initiation modes, the nucleotide addition cycle (NAC) in the RdRP elongation phase probably follows consistent mechanisms. In this chapter, representative structures of picornavirus RdRP elongation complexes are used to illustrate RdRP NAC mechanisms. In the pre-chemistry part of the NAC, RdRPs utilize a unique palm domain-based active site closure that can be further decomposed into two sequential steps. In the post-chemistry part of the NAC, the translocation process is stringently controlled by the RdRP-specific motif G, resulting in asymmetric movements of the template-product RNA. Future efforts to elucidate regulation/interventionmechanisms by mismatched NTPs or nucleotide analog antivirals are necessary to achieve comprehensive understandings of viral RdRP NAC.