Segmented negative-sense RNA viruses (sNSRVs) encode a single-polypeptide polymerase (L protein) or a heterotrimeric polymerase complex to cannibalize host messenger RNA cap structures serving as primers of transcription, and catalyse RNA synthesis. Here, we report the full-length structure of the severe fever with thrombocytopaenia syndrome virus (SFTSV) L protein, as determined by cryogenic electron microscopy at 3.4 Å, leading to an atomic model harbouring three functional parts (an endonuclease, an RNA-dependent RNA polymerase and a cap-binding domain) and two structural domains (an arm domain with a blocker motif and a carboxy-terminal lariat domain). The SFTSV L protein has a compact architecture in which its cap-binding pocket is surprisingly occupied by an Arg finger of the blocker motif, and the endonuclease active centre faces back towards the cap-binding pocket, suggesting that domain rearrangements are necessary to acquire the pre-initiation state of the active site. Our results provide insight into the complete architecture of sNSRV-encoded L protein and further the understanding of sNSRV transcription initiation.

中文翻译：

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严重发热伴血小板减少综合征病毒L蛋白的结构阐明了病毒转录起始的机制。

分段负义 RNA 病毒 (sNSRVs) 编码单多肽聚合酶 (L 蛋白) 或异源三聚体聚合酶复合物，以蚕食作为转录引物的宿主信使 RNA 帽结构，并催化 RNA 合成。在这里，我们报告了严重发热伴血小板减少综合征病毒 (SFTSV) L 蛋白的全长结构，该结构通过 3.4 Å 的低温电子显微镜测定，导致具有三个功能部分的原子模型（核酸内切酶、RNA 依赖性RNA 聚合酶和一个帽结合结构域）和两个结构域（一个带有阻断基序的臂结构域和一个羧基末端套索结构域）。SFTSV L 蛋白具有紧凑的结构，其中它的帽结合口袋令人惊讶地被阻断基序的 Arg 指占据，并且内切核酸酶活性中心面向帽结合口袋，表明结构域重排对于获得活性位点的预起始状态是必要的。我们的结果提供了对 sNSRV 编码 L 蛋白完整结构的深入了解，并进一步了解了 sNSRV 转录起始。