在Candida albicans中预测CUG编码翻译对未表征蛋白的结构效应
Michaela Čermáková1, Olga Heidingsfeld1,2
1Department of Biochemistry, Faculty of Science, Charles University in Prague, Hlavova 2030, 128 43 Prague, Czech Republic.
Journal of fungi (Basel, Switzerland)
|September 26, 2025
概括
病原性酵母 Candida albicans 可以误读 CUG 编码子,导致不稳定的蛋白质组. 这项研究使用AlphaFold2来预测基本蛋白质中氨酸替代物的结构影响,在大多数情况下发现最小的变化.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 计算生物学 计算生物学
背景情况:
- 标准的遗传密码将CUG翻译为白,但CTG类酵母如Candida albicans使用非标准的代码.
- 在这些酵母中,CUG编码子主要转化为血清素 (95-97%),偶尔转化为白素 (3-5%),从而造成蛋白质组的不稳定.
- 蛋白质中的氨酸氨酸替代物的功能和结构后果尚不清楚,特别是在必需基因中.
研究的目的:
- 通过使用计算建模来研究Candida albicans中12种必需蛋白质中氨酸替代氨酸的潜在结构影响.
- 评估这些由CUG码子模糊性引起的氨基酸替代是否影响蛋白质结构和功能.
主要方法:
- 利用AlphaFold2,一个基于深度学习的蛋白质结构预测工具.
- 分析了来自Candida albicans的12种必需蛋白质,这些蛋白质在其他酵母和人类基因组中缺乏同类.
- 对比野生类型蛋白质 (含氨酸) 的预测结构与氨酸在通常由氨酸占据的位置的变体.
主要成果:
- 由于分析蛋白质的同质性较低,AlphaFold2预测的可靠性较低.
- 分析的蛋白质根据在氨酸与氨酸交换后观察到的结构结果进行了分类.
- 在12种蛋白质中,仅在4种蛋白质中观察到显著的结构变化;剩下的8种蛋白质在血清蛋白和白蛋白变体之间没有显著的结构差异.
结论:
- 由于Candida albicans中CUG码子模糊性导致的氨酸-白氨酸替代物似乎对大多数研究的基本蛋白质具有有限的结构影响.
- 这项研究表明,由于这种遗传密码变异,蛋白质组的不稳定性可能并不总是导致蛋白质结构发生剧烈变化.
- 需要进一步的实验验证,才能充分阐明这些微妙或不存在的基本蛋白质结构变化的功能影响.
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