病毒组中的蛋白质折叠和功能的诞生
Jason Nomburg1,2,3, Erin E Doherty3,4, Nathan Price1,2,3
1Gladstone-UCSF Institute of Data Science and Biotechnology, San Francisco, CA, USA.
Nature
|August 26, 2024
概括
一个新的数据库揭示了许多病毒蛋白缺乏已知的结构. 研究人员发现病毒蛋白中保留的机制通过向循环GMP-AMP (cGAMP) 来逃避宿主免疫力.
科学领域:
- 病毒学
- 结构生物学
- 免疫学
背景情况:
- 由于序列的分歧,病毒迅速进化,产生具有未知的功能的蛋白质.
- 在现有的数据库中,很大一部分病毒蛋白缺乏可识别的结构对应物.
研究的目的:
- 分析病毒蛋白的结构多样性并确定潜在的功能.
- 研究病毒与宿主相互作用的保存机制,特别是免疫规避.
主要方法:
- 构建和分析来自4,463种真核生物病毒的67,715个预测蛋白质结构的数据库.
- 与已知的蛋白质进行结构比较,包括AlphaFold数据库中的蛋白质.
- 对已识别的蛋白质功能进行实验验证,重点是免疫逃避途径.
主要成果:
- 62% 的病毒蛋白质在结构上是独一无二的,缺乏 AlphaFold 同类物质.
- 在病毒蛋白和宿主蛋白之间发现了结构上的相似性,这表明它们具有共同的功能.
- 在未注释的病毒蛋白质中,已确定25%的假定功能,包括免疫逃避.
- 鉴定出RNA连接酶T类基酶是循环GMP-AMP (cGAMP) 的水解基因,它是菌体和真核病毒中保存的免疫逃避机制.
结论:
- 一个新的病毒蛋白结构数据库提供了关于病毒与宿主相互作用的见解.
- 通过RNA连接酶T介导的cGAMP水解是一种进化保存的病毒免疫逃避策略.
- 这项工作为识别整个病毒组的共同机制开辟了道路.
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