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SARS-CoV-2复制-转录复合物中解旋酶-聚合酶偶联的结构基础获解析
2020-07-31 13:54

美国洛克菲勒大学Elizabeth A. Campbell、Seth A. Darst等研究人员合作,解析出SARS-CoV-2复制-转录复合物中解旋酶-聚合酶偶联的结构基础。相关论文于2020年7月28日在线发表于《细胞》。

研究人员表示,SARS-CoV-2基因组通过依赖RNA的RNA聚合酶全酶(亚基nsp7/nsp82/nsp12)与一系列辅助因子一起复制和转录。其中一个因子是nsp13解旋酶。holo-RdRp和nsp13都是病毒复制所必需的,并且是治疗COVID-19疾病的靶标。
 
研究人员报道了SARS-CoV-2 holo-RdRp的冷冻电镜结构,该结构含有一个RNA模板产物,并与两个nsp13解旋酶分子形成复合物。每个nsp13的N末端结构域与nsp8每个拷贝的N末端延伸相互作用。nsp13也与nsp12-thumb相互作用。该结构将解旋酶的核酸结合ATPase域直接置于复制转录的Hol-RdRp的前面。研究人员还观察到ADP-Mg2+结合在nsp12 N末端Nidovirus RdRp相关核苷酸转移酶域中。
 
附:英文原文

Title: Structural basis for helicase-polymerase coupling in the SARS-CoV-2 replication-transcription complex

Author: James Chen, Brandon Malone, Eliza Llewellyn, Michael Grasso, Patrick M.M. Shelton, Paul Dominic B. Olinares, Kashyap Maruthi, Ed T. Eng, Hasan Vatandaslar, Brian T. Chait, Tarun Kapoor, Seth A. Darst, Elizabeth A. Campbell

Issue&Volume: 2020-07-28

Abstract: SARS-CoV-2 is the causative agent of the 2019-2020 pandemic. The SARS-CoV-2 genome is replicated and transcribed by the RNA-dependent RNA polymerase holoenzyme (subunits nsp7/nsp82/nsp12) along with a cast of accessory factors. One of these factors is the nsp13 helicase. Both the holo-RdRp and nsp13 are essential for viral replication and are targets for treating the disease COVID-19. Here we present cryo-electron microscopic structures of the SARS-CoV-2 holo-RdRp with an RNA template-product in complex with two molecules of the nsp13 helicase. The Nidovirus-order-specific N-terminal domains of each nsp13 interact with the N-terminal extension of each copy of nsp8. One nsp13 also contacts the nsp12-thumb. The structure places the nucleic acid-binding ATPase domains of the helicase directly in front of the replicating-transcribing holo-RdRp, constraining models for nsp13 function. We also observe ADP-Mg2+ bound in the nsp12 N-terminal nidovirus RdRp-associated nucleotidyltransferase domain, detailing a new pocket for anti-viral therapeutic development.

DOI: 10.1016/j.cell.2020.07.033

Source: https://www.cell.com/cell/fulltext/S0092-8674(20)30941-7

Cell:《细胞》,创刊于1974年。隶属于细胞出版社,最新IF:36.216
官方网址:https://www.cell.com/
投稿链接:https://www.editorialmanager.com/cell/default.aspx

本期文章:《细胞》:Online/在线发表

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