A novel mechanism to ensure terminal initiation by hepatitis C virus NS5B polymerase
A novel mechanism to ensure terminal initiation by hepatitis C virus NS5B polymerase
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DOI：
10.1006/viro.2001.0948
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发表时间：
2001-06-20
期刊：
影响因子：
3.7
通讯作者：
Zhong, WD
中科院分区：
文献类型：
--
作者：
Hong, Z;Cameron, CE;Zhong, WD
丙型肝炎病毒(HCV)非结构蛋白5B(NS5B)依赖RNA的RNA聚合酶(RdRp)在拇指亚区获得了一个独特的β-发夹，该β-发夹在定位病毒RNA基因组的3‘末端以正确启动复制方面起着重要作用。该β-发夹的存在干扰了聚合酶与预退火双链RNA(DsRNA)分子的结合，并仅允许RNA模板的单链3’末端有效地与活性部位结合。我们认为，这个β-发夹可能作为一种“门”，防止模板RNA的3‘端滑过活性部位，并确保从基因组末端开始复制。这一假设得到了利用dsRNA底物并在内部启动RNA合成的β-发夹缺失突变体的能力的支持。所提出的末端起始机制可能代表了丙型肝炎病毒和相关病毒采用的一种新的复制策略。(C)2001年学术出版社。
Hepatitis C virus (HCV) nonstructural protein 5B (NS5B) RNA-dependent RNA polymerase (RdRp) has acquired a unique beta -hairpin in the thumb subdomain which protrudes toward the active site, We report here that this beta -hairpin plays an important role in positioning the 3 ' terminus of the viral RNA genome for correct initiation of replication The presence of this beta -hairpin interferes with polymerase binding to preannealed double-stranded RNA (dsRNA) molecules and allows only the single-stranded 3 ' terminus of an RNA template to bind productively to the active site, We propose that this beta -hairpin may serve as a "gate" which prevents the 3 ' terminus of the template RNA from slipping through the active site and ensures initiation of replication from the terminus of the genome. This hypothesis is supported by the ability of a beta -hairpin deletion mutant that utilizes dsRNA substrates and initiates RNA synthesis internally. The proposed terminal initiation mechanism may represent a novel replication strategy adopted by HCV and related viruses. (C) 2001 Academic Press.