在牛皮和免疫失调中具有潜在作用的RNF114 nsSNP的计算识别
Ghalia Mahfod Aldoseri1, Arwa Ibrahim Alwabran1, Ghanem Mahfod Aldoseri1
1College of Medicine, Prince Sattam bin Abdulaziz University, Al-Kharj 16278, Saudi Arabia.
Medical sciences (Basel, Switzerland)
|September 22, 2025
概括
三种新的RNF114基因变异可能导致像牛皮这样的免疫疾病. 这些突变使RNF114蛋白质不稳定,可能导致免疫失调和自身免疫性疾病.
科学领域:
- 遗传学和分子生物学
- 免疫学 免疫学 免疫学
- 生物信息学是一种生物信息学.
背景情况:
- RNF114基因编码一种E3泛素连酶,它对免疫信号传递和炎症调节至关重要.
- 在RNF114中,非同义单核酸多态 (nsSNP) 可能会损害蛋白质功能,导致诸如牛皮之类的免疫疾病.
- RNF114 nsSNP的结构和功能后果在很大程度上仍未被描述.
研究的目的:
- 通过全面的生物信息学分析,研究 RNF114 nsSNP 的功能和结构影响.
- 为了识别与免疫失调相关的潜在致病性RNF114变体.
主要方法:
- 使用了多种生物信息学工具 (SIFT,PolyPhen-2,PROVEAN等) 为了预测nsSNP的有害性.
- 使用I-Mutant2.0和MUpro.0评估了蛋白质稳定性的变化.
- 使用AlphaFold进行结构建模,并使用UCSF ChimeraX进行可视化.
- 分析了残留物保护 (ConSurf) 和蛋白质与蛋白质相互作用 (STRING).
主要成果:
- 确定了三个nsSNP (C49R,R68C,R68H),所有测试工具都预测它们是有害和破坏稳定的.
- 这些变异发生在高度保存的残留物中,并显著破坏RNF114蛋白质结构的稳定.
- 结构建模揭示了RNF114域架构中的中断.
- STRING分析突出了RNF114与免疫调节者的相互作用以及NF-κB信号传递,蛋白质分解和自身免疫通路的参与.
结论:
- 预测了三种新的RNF114变体 (C49R,R68C,R68H),具有显著的蛋白质破坏效应.
- 这些变体具有潜在的病原性,可能导致免疫失调和自身免疫性疾病.
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