ATP11C Q79E突变体的冷EM结构揭示了改变脂识别的结构基础
Yuheng Qian1, Chai C Gopalasingam2, Christoph Gerle3
1Department of Chemistry, Faculty of Science, Hokkaido University, Japan; Graduate School of Pharmaceutical Sciences, Nagoya University, Nagoya, Japan.
The Journal of biological chemistry
|November 14, 2025
概括
在P4-ATPase ATP11C (Q79E) 中的一次突变扩大了其基质特异性,包括酸丁胆 (PC). 这种由cryo-EM揭示的结构变化,解释了突变如何改变脂酸转酶活性.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 细胞生物学 细胞生物学
背景情况:
- P4-ATPases ATP11A和ATP11C是哺乳动物等离子体膜中的关键脂转酶.
- 它们对氨酸氨酸 (PS) 和氨酸乙醇胺 (PE) 具有严格的特异性,保持了膜不对称性.
- 在ATP11A中发生的突变 (Q84E) 改变了其特异性,包括酸丁胆 (PC).
研究的目的:
- 调查ATP11C P4-ATPase中改变基质特异性的结构基础.
- 了解单点突变如何影响脂基质的基底特异性.
主要方法:
- 使用冷电子显微镜 (cryo-EM) 来确定ATP11C Q79E突变的结构.
- 进行了ATPase活性测定,以测量野生类型和突变酶的基质特异性.
主要成果:
- ATP11C Q79E突变体显示保留了依赖PS的活性,并获得了强大的依赖PC的活性.
- 冷EM揭示了在E2-Pi状态的重塑结合口袋中的PC分子.
- 突变引发了形状变化,为PC头部组创造了空间.
结论:
- 一个单点突变 (Q79E) 可以显著改变P4-ATPases的基质特异性.
- 结构洞察力解释了ATP11C如何适应酸丁胆,扩大其翻转酶的能力.
- 这项研究提供了对脂运输蛋白质基质特异性的分子理解.
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