在dRNA病毒内部的细分基因组和RNA聚合酶复合物的现场结构
Xing Zhang1, Ke Ding2,3, Xuekui Yu2
1California Nanosystems Institute, Los Angeles, CA 90095, USA.
Nature
|October 28, 2015
概括
研究人员揭示了细胞质多面体病毒 (CPV) 中的转录酶复合体 (TEC) 的结构. 这种复合物对病毒RNA合成至关重要,在环境线索下改变形状以激活转录.
科学领域:
- 结构病毒学
- 分子生物学
- 病毒RNA转录
背景情况:
- 包括轮状病毒和细胞质多重体病毒 (CPV) 在内的Reoviridae家族中的病毒具有细分的双链RNA (dsRNA) 基因组.
- 这些病毒在它们的体内使用转录酶复合体 (TEC) 内合成传递 RNA (mRNA).
研究的目的:
- 确定静止CPV (q-CPV) 中的dsRNA基因组的组织.
- 在静止 (q-CPV) 和转录 (t-CPV) 状态下阐明TEC的现场原子结构.
主要方法:
- 直接电子计数冷电子显微镜
- 不对称的重建技术.
- 病毒组件的结构分析.
主要成果:
- 十个细分的dsRNA与十个TEC组织非对称,每个dsRNA细分直接连接到一个TEC.
- TEC包括两个相互作用的子单元:依赖RNA的RNA聚合酶 (RdRP) 和NTPase VP4.
- 在从q-CPV转换为t-CPV时,RdRP手域的构造变化会产生RNA模板输入通道并激活聚合酶活性位点.
- 体外蛋白 (CSP) 子单元与VP4和RdRP相互作用,将外部提示传感与TEC激活联系起来.
结论:
- 这项研究揭示了dRNA基因组和TEC在CPV中的精确组织.
- 结构洞察力表明TEC激活的机制,涉及RdRP的结构变化.
- 这些发现确定了囊蛋白对外部环境的感知与病毒RNA转录的启动之间的联系.
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