Structure of the Vesicular Stomatitis Virus L Protein in Complex with Its Phosphoprotein Cofactor
Structure of the Vesicular Stomatitis Virus L Protein in Complex with Its Phosphoprotein Cofactor
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DOI：
10.1016/j.celrep.2019.12.024
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发表时间：
2020-01-07
期刊：
影响因子：
8.8
通讯作者：
Harrison, Stephen C.
中科院分区：
文献类型：
--
作者：
Jenni, Simon;Bloyet, Louis-Marie;Harrison, Stephen C.
非节段负链RNA病毒的大（L）蛋白是多功能酶，其产生加帽的、甲基化的和聚腺苷酸化的mRNA并复制病毒基因组。磷蛋白（P），从病毒核糖核蛋白（RNP）模板的有效RNA依赖性RNA聚合所需的，调节L蛋白的功能和构象。我们报告的结构水泡性口炎病毒L在复杂的P辅因子确定在3.0埃的分辨率，通过电子冷冻显微镜，使我们能够可视化绑定段的P.三个P段与多个L域的接触显示P如何诱导一个封闭的，紧凑的，启动能力的构象。P与L的结合将其N-末端结构域定位在推定的RNA出口通道附近，用于新合成的基因组与核蛋白的有效结合，并将其C-末端结构域定向为与RNP模板相互作用。该模型显示，引发环中的保守色氨酸可以支持起始5'核苷酸。
The large (L) proteins of non-segmented, negative-strand RNA viruses are multifunctional enzymes that produce capped, methylated, and polyadenylated mRNA and replicate the viral genome. A phosphoprotein (P), required for efficient RNA-dependent RNA polymerization from the viral ribonucleoprotein (RNP) template, regulates the function and conformation of the L protein. We report the structure of vesicular stomatitis virus L in complex with its P cofactor determined by electron cryomicroscopy at 3.0 angstrom resolution, enabling us to visualize bound segments of P. The contacts of three P segments with multiple L domains show how P induces a closed, compact, initiation-competent conformation. Binding of P to L positions its N-terminal domain adjacent to a putative RNA exit channel for efficient encapsidation of newly synthesized genomes with the nucleoprotein and orients its C-terminal domain to interact with an RNP template. The model shows that a conserved tryptophan in the priming loop can support the initiating 5' nucleotide.