对Mus GPR4和Xenopus GPR4的质子传感的演化研究和结构基础
Xin Wen1, Pan Shang2, Haidi Chen3
1Key Laboratory Experimental Teratology of the Ministry of Education, New Cornerstone Science Laboratory, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong 250012, China; NHC Key Laboratory of Otorhinolaryngology, Qilu Hospital of Shandong University, Advanced Medical Research Institute, Shandong University, Jinan, China.
Cell
|January 3, 2025
概括
这项研究揭示了G蛋白结合受体4 (GPR4) 如何感知动物的pH值. 结构分析揭示了质子感应的共同和独特机制,
科学领域:
- 生物化学
- 结构生物学
- 进化生物学
背景情况:
- 动物利用像G蛋白合受体4 (GPR4) 这样的pH感应膜受体进行生理调节.
- GPR4的进化历史和精确的质子感应机制尚未完全理解.
研究的目的:
- 通过GPR4阐明质子传感的进化轨迹和结构基础.
- 研究GPR4活动的最佳pH值与特定物种的血液pH值之间的相关性.
主要方法:
- 在不同pH值下确定了Xenopus tropicalis GPR4 (xtGPR4) 和Mus musculus GPR4的7电子显微镜 (cryo-EM) 结构.
- 分析了对GPR4激活负责的结构变化和质子位点.
主要成果:
- 在GPR4的最佳pH和不同物种的血液pH之间观察到正相关性.
- 特定残留物的质子化 (HECL2-45.47和H7.36) 建立了极性网络并稳定了GPR4结构,这是一个保存的激活机制.
- 在xtGPR4中,HECL2-45.41的明显质子化解释了其更酸的最佳pH值.
结论:
- 在各个物种中,GPR4的质子传感由共同和独特的结构机制控制.
- 这些发现为pH感应受体的结构-功能-演变关系提供了洞察力.
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