生物
复制子
核糖核酸
RNA依赖性RNA聚合酶
病毒学
RNA聚合酶
病毒复制
病毒结构蛋白
基因组
病毒蛋白
抄写(语言学)
复式(建筑)
遗传学
病毒
病毒进入
DNA
基因
哲学
语言学
作者
Harry M. Williams,S. Thorkelsson,Dominik Vogel,Morlin Milewski,Carola Busch,Stephen Cusack,Kay Grünewald,Emmanuelle R. J. Quemin,Maria Rosenthal
摘要
Severe fever with thrombocytopenia syndrome virus (SFTSV) is a phenuivirus that has rapidly become endemic in several East Asian countries. The large (L) protein of SFTSV, which includes the RNA-dependent RNA polymerase (RdRp), is responsible for catalysing viral genome replication and transcription. Here, we present 5 cryo-electron microscopy (cryo-EM) structures of the L protein in several states of the genome replication process, from pre-initiation to late-stage elongation, at a resolution of up to 2.6 Å. We identify how the L protein binds the 5' viral RNA in a hook-like conformation and show how the distal 5' and 3' RNA ends form a duplex positioning the 3' RNA terminus in the RdRp active site ready for initiation. We also observe the L protein stalled in the early and late stages of elongation with the RdRp core accommodating a 10-bp product-template duplex. This duplex ultimately splits with the template binding to a designated 3' secondary binding site. The structural data and observations are complemented by in vitro biochemical and cell-based mini-replicon assays. Altogether, our data provide novel key insights into the mechanism of viral genome replication by the SFTSV L protein and will aid drug development against segmented negative-strand RNA viruses.
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