计算分析在ATG10中识别了致病性nsSNP,ATG10是自性通路的E2类乌比奎丁结合酶
Arpna1, Ali Gharib Gharib2, Arti Sharma2
1Department of Molecular Biology and Biochemistry, Guru Nanak Dev University, Amritsar, 143 005, Punjab, India.
International journal of biological macromolecules
|December 29, 2025
概括
与自相关的基因10 (Atg10) 突变会影响蛋白质的稳定性和相互作用,为癌症和神经退行性疾病等疾病提供潜在的分子标记物. 这些发现指导了未来的诊断和治疗策略.
科学领域:
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
- 生物化学 生物化学
背景情况:
- 自相关基因10 (Atg10) 是自细胞形成中的关键的E2类酶,对于Atg12-Atg5结合和MAP-LC3脂化至关重要.
- Atg10在各种癌症,神经退行性疾病和与自相关的疾病中发挥作用,单核酸多态性 (SNP) 与疾病倾向有关.
研究的目的:
- 使用in silico工具调查Atg10的分子特征,以确定潜在的分子标记物.
- 分析ATG10中有害的非同义SNP (nsSNP) 以及它们对蛋白质结构,稳定性和相互作用的潜在影响.
主要方法:
- 在ATG10.0中对有害的nsSNP进行了体分析.
- 使用像MutPred2.2这样的工具预测影响Atg10稳定性和灵活性的突变.
- 分子动力学 (MD) 模拟来评估由突变引起的结构变化.
- 监管要素的识别,包括转录因子结合点和翻译后修改点.
主要成果:
- 发现11种突变影响了Atg10的稳定性,6种突变增加了分子灵活性.
- 在催化域中,Y112N,P154L和C166Y突变显示出高致病性 (>0.9).
- MD模拟表明,随着这些突变,Atg10结构的稳定性发生变化.
- 结构分析显示了在催化环境中保存的E2酶配置.
- 预测的调节元素包括33个转录因子位点,13个酸化位点,2个SUMOylation位点和2个ubiquitination位点.
结论:
- 在ATG10中识别的误解SNP可以作为潜在的分子标记物.
- 这些SNP可能是蛋白质组研究,诊断方法和自相关疾病治疗策略的有价值的目标.
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