Spf1和Ste24:在真核细胞细胞中超膜蛋白质拓学的质量控制器
Donald J Tipper1, Carol A Harley2,3
1University of Massachusetts Medical School, Worcester, MA, United States.
Frontiers in cell and developmental biology
|August 28, 2023
概括
单核细胞跨膜蛋白的插入往往是不正确的. 酵母突变揭示了Spf1和Ste24蛋白质是保存质量控制系统的关键组成部分,该系统可纠正这些错误,确保蛋白质的正确功能.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 贩卖蛋白质 贩卖蛋白质 是一个问题.
背景情况:
- 细胞DNA复制,转录和翻译表现出高保真度.
- 然而,大约33%的人类蛋白质组,跨膜 (TM) 蛋白质,经常被插入错误的拓.
- 正确的TM蛋白质拓对于细胞功能和局部化至关重要,受正内部规则 (PIR) 的支配,该规则指导正电荷残留物.
研究的目的:
- 为了研究在真核细胞中纠正异常TM蛋白质拓学的基础上的分子机制.
- 识别和描述在TM蛋白插入过程中维持正内部规则 (PIR) 的遗传因素.
- 阐明Spf1和Ste24蛋白质在TM蛋白质拓学的保存质量控制系统中的作用.
主要方法:
- 酵母 (Saccharomyces cerevisiae) 突变的选择显示了TM蛋白的增加插入,这与PIR相反.
- 鉴定出突变的基因分析和表型特征,重点是SPF1和STE24.
- 生物化学和细胞生物学研究Spf1/Atp13A1和Ste24在TM蛋白位移和加工中的拟议功能.
主要成果:
- 只有在SPF1和STE24中发现了具有强烈的TM蛋白插入错误表型的酵母突变.
- 发现Spf1 / Atp13A1可以将在PIR上插入的TM蛋白脱而出,从而使其重新插入.
- 建议Spf1和Ste24形成一个保存的PIR质量控制系统,纠正大约75%的PIR违规行为.
结论:
- Spf1 和 Ste24 作为 TM 蛋白质拓学的保存真核细胞质量控制系统,执行 PIR.
- 这种系统很可能是从 prokaryotic 祖先进化而来的,在 ER 蛋白质质量控制中与 UPR,ERAD 和 ER-phagy 一起起起关键作用.
- 了解这个系统对于理解细胞平衡和蛋白质生物生成至关重要.
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