小柯机器人

美国埃默里大学梁波研究小组解析出启动子结合的呼吸道合胞病毒聚合酶结构。相关论文于2023年12月20日在线发表在《自然》杂志上。

研究人员表示，呼吸道合胞病毒（RSV）聚合酶是一种多功能RNA依赖性RNA聚合酶，由大蛋白（L）和磷蛋白（P）组成。它将RNA基因组转录成十条病毒mRNA，并复制全长病毒基因组和抗原组RNA。RSV聚合酶通过与基因组或抗原组保守的3′端RNA启动子结合来启动RNA合成。然而，由于缺乏RSV聚合酶与RNA启动子结合的结构，阻碍了对RSV RNA合成机理的了解。

研究人员报告了RSV聚合酶与其基因组和反基因组病毒RNA启动子结合的冷冻电镜结构，这是RNA依赖性RNA聚合酶与其RNA启动子复合物在非片段负义RNA病毒中的首次结构。与启动子结合的RSV聚合酶整体结构与未结合（apo）的聚合酶相似。这些结构说明了RSV聚合酶与RNA启动子之间的相互作用，并为在RSV启动子第1和第3位启动RNA合成提供了结构基础。这些结构加深了人们对RSV聚合酶启动前状态的理解，有助于针对RSV的抗病毒研究。

附：英文原文

Title: Structures of the promoter-bound respiratory syncytial virus polymerase

Author: Cao, Dongdong, Gao, Yunrong, Chen, Zhenhang, Gooneratne, Inesh, Roesler, Claire, Mera, Cristopher, DCunha, Paul, Antonova, Anna, Katta, Deepak, Romanelli, Sarah, Wang, Qi, Rice, Samantha, Lemons, Wesley, Ramanathan, Anita, Liang, Bo

Issue&Volume: 2023-12-20

Abstract: The respiratory syncytial virus (RSV) polymerase is a multifunctional RNA-dependent RNA polymerase composed of the large (L) protein and the phosphoprotein (P). It transcribes the RNA genome into ten viral mRNAs and replicates full-length viral genomic and antigenomic RNAs1. The RSV polymerase initiates RNA synthesis by binding to the conserved 3′-terminal RNA promoters of the genome or antigenome2. However, the lack of a structure of the RSV polymerase bound to the RNA promoter has impeded the mechanistic understanding of RSV RNA synthesis. Here we report cryogenic electron microscopy structures of the RSV polymerase bound to its genomic and antigenomic viral RNA promoters, representing two of the first structures of an RNA-dependent RNA polymerase in complex with its RNA promoters in non-segmented negative-sense RNA viruses. The overall structures of the promoter-bound RSV polymerases are similar to that of the unbound (apo) polymerase. Our structures illustrate the interactions between the RSV polymerase and the RNA promoters and provide the structural basis for the initiation of RNA synthesis at positions 1 and 3 of the RSV promoters. These structures offer a deeper understanding of the pre-initiation state of the RSV polymerase and could aid in antiviral research against RSV.

DOI: 10.1038/s41586-023-06867-y

Source: https://www.nature.com/articles/s41586-023-06867-y

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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