从到硫:预测建模揭示了蛋白的构造和结合变化
Shiqi Luo1, Xinnan Liu2, Xia Wang1
1State Key Laboratory of Complex, Severe, and Rare Diseases, Department of Immunology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China.
Journal of structural biology
|December 11, 2025
概括
研究人员使用AlphaFold 3来创建所有人类蛋白的原子模型,揭示了对依赖途径和潜在药物标的结构洞察力.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 基因组学就是基因组学.
背景情况:
- 含有第21个氨基酸氨基 (Sec) 的蛋白质对于氧化还原,内分泌和代谢功能至关重要.
- 高分辨率结构仅适用于25个人类蛋白家族成员中的少数几个.
研究的目的:
- 使用AlphaFold 3 (AF3) 为所有人类蛋白生成全面的全长原子模型.
- 为了研究单半氨酸 (Sec) 替代半氨酸 (Cys) 对单蛋白结构和功能的结构影响.
- 为了解依赖的氧化还原生物学建立结构基础.
主要方法:
- 利用AlphaFold 3 (AF3) 来预测所有25种人类蛋白的原子模型.
- 生成的in-silico Sec-to-Cys变体用于比较结构分析.
- 采用基于结构的聚类来识别保存的结构图案.
主要成果:
- AF3生成了22种烯蛋白的高可信度模型,对谷氨过氧化酶4 (GPX4) 有亚协议.
- 在19种蛋白质中,Sec-to-Cys替代保留了整体折叠,但在6种蛋白质中改变了基硫化物链接.
- 在15种蛋白中发现了一种保存的"Se-thioredoxin-like"核心.
- AF3预测了GPX4的同位体组合,与实验观测一致.
结论:
- AF3生成的模型形成了人类蛋白质组的全面结构图谱.
- 这些模型阐明了Sec的折叠特定定位及其在蛋白质结构中的作用.
- 该数据集作为机理学研究,进化分析和在依赖的氧化还原生物学中药物设计的基础.
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