设计化石,模拟细菌铁素折叠的进化
Bhanu P Jagilinki1,2, Ian Campbell3, Alexei M Tyryshkin1,2
1Center for Advanced Biotechnology and Medicine and the Department of Biochemistry and Molecular Biology, Robert Wood Johnson Medical School, Rutgers University, Piscataway, New Jersey 08854, United States.
JACS Au
|November 28, 2025
概括
研究人员使用结构引导设计建模了古代蛋白质进化的模型. 设计的"化石"蛋白质称为半素显示出氧气敏感性,与现代铁素不同,表明早期的生命形式适应了不断变化的环境.
科学领域:
- 生物化学和分子进化
- 生命的起源研究 生命的起源研究
- 蛋白质工程是指蛋白质工程.
背景情况:
- 电子转移对新陈代谢至关重要,它依赖于蛋白质电子载体,这些载体可能在生命历史的早期出现.
- 小细菌铁硫结合铁毒素是古老的蛋白质,它们的当前结构表明古老的基因重复事件.
- 铁素的进化历史早于氨基酸序列的遗传学分析,需要替代的重建方法.
研究的目的:
- 通过模拟祖先的蛋白质阶段来重建铁素的深远分子历史.
- 调查假设的祖先铁素形式的功能和结构性质,称为半素和同素.
主要方法:
- 利用结构导向蛋白质设计创建祖先铁素形式 (半素和同素) 的计算模型.
- 评估设计的半多克辛和共多克辛的结构,热力学和电化学行为.
- 使用体内电子转移补充试验来评估在不同氧气条件下细菌生长中的蛋白质功能.
主要成果:
- 设计的半多克辛表现出结构,热力学和电化学特性类似于它们的共多克辛对应物.
- 在体内测试显示,与symdoxins相比,semidoxins对细菌生长具有更大的氧气敏感性.
- 在无氧微生物中识别自然存在的半素,与在设计的半素中观察到的氧气敏感性相一致.
结论:
- 模拟的半素代表了铁素进化的合理祖先阶段,为早期蛋白质适应提供了洞察力.
- 半多克辛和共多克辛之间的不同氧气敏感性表明与环境氧气水平相关的进化压力.
- 自然半素的存在及其单体-二元平衡暗示了与更简单的铁硫结合的潜在联系.
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