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.
bioRxiv : the preprint server for biology
|July 9, 2025
概括
结构生物信息学揭示了六个毒素超级家族的共同进化历史,以前被快速序列进化所隐藏. 这项研究确定了一种新的"双指毒素"折叠和一大群原生体中的相关蛋白质.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 进化生物学 进化生物学
背景情况:
- 有毒动物拥有具有制药潜力的多种毒素,但快速进化使进化关系推断复杂化.
- 甲的毒素是类毒素,其快速演变挑战了基于序列的进化分析.
研究的目的:
- 通过结构生物信息学来确定六种共毒素超级家族之间的进化关系.
- 识别和描述一种新的蛋白质折叠及其在原生细胞中的分布.
主要方法:
- 核磁共振 (NMR) 结构确定宏毒素Tx33.1.1.
- 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的NMR结构,揭示了一个新的"两指毒素" (2FTX) 折叠.
- 结构比较发现了Tx33.1与其他五个共毒素超级家族之间的相似之处,尽管序列同样性有限,但表明了共同的进化起源.
- 在原始体中发现了一大群以前未知的2FTX蛋白质,包括结构上类似于Drosophila melanogaster的Argos的非毒性形牛蛋白质.
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.
- "双指毒素" (2FTX) 折叠是一种新发现的蛋白质折叠,在原生细胞中分布广泛.
- 许多原生体2FTX蛋白可能调节EGFR信号,类似于Argos.
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