反氧酶P4HB和PDIA3与STIM1相互作用,以微调其敏感性和激活
Yangchun Du1, Feifan Wang1, Panpan Liu1
1Beijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal University, Beijing 100875, China.
International journal of molecular sciences
|July 27, 2024
概括
蛋白质二硫化异构酶P4HB和PDIA3微调STIM1结合亲和力,调节存储运行的进入 (SOCE),对细胞信号和疾病至关重要. 这一发现揭示了STIM1的发展.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 储存运行的输入 (SOCE) 是一种由STIM1.1调解的关键流入机制.
- 失调的SOCE与自身免疫性疾病,动脉样硬化和癌症有关.
- 翻译后的修改,包括氧化,显著影响STIM1功能.
研究的目的:
- 研究ER-光蛋白二硫化异相酶 (PDI) 在调节STIM1功能中的作用.
- 阐明PDI与STIM1.1相互作用并调节的分子机制.
- 了解PDI相互作用对STIM1敏感性和SOCE的影响.
主要方法:
- 蛋白质学查以确定ER-光线STIM1相互作用体.
- 针对STIM1氨酸残留物的局部导向突变发生.
- 成像实验用于评估SOCE动态.
- 西方涂抹和共同免疫沉以确认蛋白质相互作用.
主要成果:
- 三个PDI (P4HB,PDIA3,TXNDC5) 被确定为STIM1和STIM2的ER-luminal相互作用体.
- STIM1囊残留物的突变降低了它的亲和力.
- 击败PDIA3或P4HB增加了野生型STIM1亲和力,但不是突变.
- PDIA3和P4HB调节STIM1的敏感性,在部分存储耗尽时增强SOCE.
结论:
- P4HB和PDIA3通过微调其结合亲和力来动态调节STIM1的激活.
- 这种调制调整STIM1激活水平以响应生理线索.
- STIM1介导的信号传递和细胞氧化还原反应之间的相互作用对健康和疾病有影响.
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