A molecular pore spans the double membrane of the coronavirus replication organelle.
A molecular pore spans the double membrane of the coronavirus replication organelle.
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DOI：
10.1126/science.abd3629
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发表时间：
2020-09-11
期刊：
影响因子：
--
通讯作者：
Bárcena M
中科院分区：
文献类型：
--
作者：
Wolff G;Limpens RWAL;Zevenhoven-Dobbe JC;Laugks U;Zheng S;de Jong AWM;Koning RI;Agard DA;Grünewald K;Koster AJ;Snijder EJ;Bárcena M
从冠状病毒复制细胞器输出的病毒RNA可能由冠状分子孔介导。冠状病毒将宿主细胞膜转化为特殊的双膜囊泡，长期以来一直被认为可以容纳病毒基因组复制。然而，由于这些隔室似乎是完全密封的，因此仍然不知道新制备的病毒RNA如何输出到细胞溶质中进行翻译并包装成新的病毒体。Wolff等人使用低温电子显微镜鉴定了一个跨越双膜的分子孔（参见Unchwaniwala和Ahlquist的Perspective）。一个大型冠状病毒跨膜蛋白的六个拷贝形成了这个结构的核心，这可能构成了病毒RNA输出通道，并为未来的抗病毒干预提供了靶点。《科学》，本期第1395页;另见第1395页冠状病毒基因组复制与病毒诱导的胞质双膜囊泡有关，这可能为感染细胞中的病毒RNA合成提供定制的微环境。然而，目前尚不清楚新合成的基因组和信使RNA如何从这些密封的复制区室进入胞质溶胶，以确保它们的翻译和后代病毒体的组装。在这项研究中，我们使用细胞冷冻电子显微镜可视化的分子孔复合物，跨越两个膜的双膜囊泡，并允许出口的RNA到胞质溶胶。一个大型病毒跨膜蛋白的六聚体组装被发现形成冠状复合物的核心。这种冠状病毒特异性结构可能在冠状病毒复制中起关键作用，因此构成了潜在的药物靶标。
Viral RNA exported from the coronavirus replication organelle is likely to be mediated by a crown-shaped molecular pore. Coronaviruses transform host cell membranes into peculiar double-membrane vesicles that have long been thought to accommodate viral genome replication. However, because these compartments appeared to be completely sealed, it has remained unknown how the newly made viral RNA could be exported to the cytosol for translation and packaging into new virions. Wolff et al. used cryo–electron microscopy to identify a molecular pore that spans the double membrane (see the Perspective by Unchwaniwala and Ahlquist). Six copies of a large coronavirus transmembrane protein formed the core of this structure, which may constitute a viral RNA export channel and provide a target for future antiviral interventions. Science, this issue p. 1395; see also p. Coronavirus genome replication is associated with virus-induced cytosolic double-membrane vesicles, which may provide a tailored microenvironment for viral RNA synthesis in the infected cell. However, it is unclear how newly synthesized genomes and messenger RNAs can travel from these sealed replication compartments to the cytosol to ensure their translation and the assembly of progeny virions. In this study, we used cellular cryo–electron microscopy to visualize a molecular pore complex that spans both membranes of the double-membrane vesicle and would allow export of RNA to the cytosol. A hexameric assembly of a large viral transmembrane protein was found to form the core of the crown-shaped complex. This coronavirus-specific structure likely plays a key role in coronavirus replication and thus constitutes a potential drug target.
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