来自非洲猪瘟病毒的重组RNA聚合酶的结构
Simona Pilotto1, Michal Sýkora1, Gwenny Cackett1
1Institute for Structural and Molecular Biology, Division of Biosciences, University College London, Gower Street, London, WC1E 6BT, United Kingdom.
Nature communications
|February 21, 2024
概括
非洲猪瘟病毒RNA聚合酶的结构特征,揭示了与人类RNAPII的相似之处. 这项研究为开发新抗病毒药物开发工具提供了针对ASFV的工具,ASFV对全球粮食安全构成重大威胁.
科学领域:
- 病毒学 病毒学
- 结构生物学 结构生物学
- 分子生物学分子生物学
背景情况:
- 非洲猪瘟病毒 (ASFV) 在猪中引起严重的,无法治愈的出血热,严重影响全球粮食安全.
- ASFV在细胞质中复制,利用独立于宿主细胞因子的自身转录机制,但其分子机制仍然不太清楚.
研究的目的:
- 开发生产复合ASFVRNA聚合酶 (RNAP) 的方法.
- 建立用于选ASFVRNAP抑制剂的功能测试.
- 为了确定ASFVRNAP的高分辨率冷电子显微镜 (cryo-EM) 结构.
主要方法:
- 生产复合的ASFVRNA聚合酶.
- 开发用于抑制剂查的功能性试验.
- 高分辨率冷电子显微镜 (cryo-EM) 用于结构确定.
主要成果:
- ASFV RNAP与人类RNAPII具有结构同源性,其中包括其12个子单元中的9个的真实同源.
- 关键的结构差异包括合组装平台子单元 (RPB3和RPB11) 和vRPB7.7中的一个不寻常的C端域.
- ASFV RNAP对常见的抑制剂,如利芬素和α-阿曼素,表现出耐药性.
结论:
- 具有特征的ASFV RNAP结构和重组系统为抗病毒药物设计和查提供了宝贵的平台.
- 这项研究有助于在低生物安全性封闭环境下开发抗ASFV的新疗法.
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