结构上的相似性揭示了一个扩张性的共毒毒素家族,具有双指毒素折叠
Muhammad Saad Khilji1, Celeste M Hackney1, Thomas L Koch2,3
1Department of Biology, Linderstrøm-Lang Centre for Protein Science, University of Copenhagen, Copenhagen, Denmark.
Protein science : a publication of the Protein Society
|October 11, 2025
概括
结构生物信息学揭示了六个毒素超级家族之间的进化联系. 这项研究确定了原生体中的新一类双指毒素 (2FTX) 蛋白质,可能调节EGFR信号传递.
科学领域:
- 生物化学和分子生物学
- 进化生物学 进化生物学
- 结构生物信息学 结构生物信息学
背景情况:
- 有毒动物拥有各种有毒物质,具有制药潜力.
- 像毒素这样的毒素的快速进化使得基于单独的序列的进化关系推断变得复杂.
研究的目的:
- 使用结构生物信息学阐明共毒素超级家族之间的进化关系.
- 识别和描述新的毒素结构及其进化起源.
主要方法:
- 核磁共振 (NMR) 对宏毒素的结构确定 (Tx33.1).
- 基于深度学习的结构预测和比较.
- 基因结构分析.
- 结构相似性搜索.结构相似性搜索.
主要成果:
- 解决了Tx33.1 (宏毒素) 的NMR结构.
- 在Tx33.1和五个未表征的共毒素超级家族之间发现了结构上的相似之处.
- 通过综合分析,所有六个超级家族都被证实具有共同的进化起源.
- 基于Tx33.1与Argos的结构相似性,提出了一种新的"双指毒素 (2FTX) "折叠.
- 确定了一大群原体体2FTX蛋白质,包括非毒性分泌蛋白质.
结论:
- 结构生物信息学对于发现快速进化的基因之间的进化关系至关重要.
- 一个以前未被识别的原始体2FTX蛋白质组已被确定.
- 这些2FTX蛋白可能在调节表皮生长因子受体 (EGFR) 信号传递方面发挥作用,类似于Argos.
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