Crystal structure of the Lassa virus nucleoprotein-RNA complex reveals a gating mechanism for RNA binding
Crystal structure of the Lassa virus nucleoprotein-RNA complex reveals a gating mechanism for RNA binding
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DOI：
10.1073/pnas.1108515108
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发表时间：
2011-11-29
影响因子：
11.1
通讯作者：
Saphire, Erica Ollmann
中科院分区：
文献类型：
--
作者：
Hastie, Kathryn M.;Liu, Tong;Saphire, Erica Ollmann
沙粒病毒在工业化国家和发展中国家都引起疾病。其中，出血热病毒拉沙在西非每年造成约 300,000-500,000 例感染。沙粒病毒核蛋白 (NP) 形成基因组核糖核蛋白复合物的蛋白质支架，对于病毒基因组的转录和复制至关重要。在这里，我们展示了拉沙病毒 NP 的 RNA 结合域与 ssRNA 复合物的晶体结构。该结构表明，与预测模型相反，RNA 结合在完全位于 N 末端结构域内的深层基本缝隙中。此外，本文提出的 NP-ssRNA 结构，结合氢-氘交换/MS 和功能研究，表明 NP 打开接受 RNA 的门控机制。定向诱变和功能研究为沙粒病毒纳米粒子如何结合和保护病毒基因组提供了独特的视角，并提出了病毒核糖核蛋白复合物可能的组装方式。
Arenaviruses cause disease in industrialized and developing nations alike. Among them, the hemorrhagic fever virus Lassa is responsible for similar to 300,000-500,000 infections/y in Western Africa. The arenavirus nucleoprotein (NP) forms the protein scaffold of the genomic ribonucleoprotein complexes and is critical for transcription and replication of the viral genome. Here, we present crystal structures of the RNA-binding domain of Lassa virus NP in complex with ssRNA. This structure shows, in contrast to the predicted model, that RNA binds in a deep, basic crevice located entirely within the N-terminal domain. Furthermore, the NP-ssRNA structures presented here, combined with hydrogen-deuterium exchange/MS and functional studies, suggest a gating mechanism by which NP opens to accept RNA. Directed mutagenesis and functional studies provide a unique look into how the arenavirus NPs bind to and protect the viral genome and also suggest the likely assembly by which viral ribonucleoprotein complexes are organized.