人类甜味受体的结构和功能特征
Zongjun Shi1,2, Weixiu Xu1, Lijie Wu1
1iHuman Institute, ShanghaiTech University, Shanghai, China.
Nature
|June 24, 2025
概括
研究人员使用冷EM绘制了人类甜味受体 (TAS1R2/TAS1R3). 结构揭示了糖如何与TAS1R2结合,解释了甜味的感知,并指导了新的甜味剂设计.
科学领域:
- 生物化学
- 分子生物学
- 结构生物学
背景情况:
- 甜味对饮食选择和新陈代谢健康至关重要.
- 人类甜味受体 (TAS1R2/TAS1R3) 是一种感知各种甜味化合物的C类GPCR.
- 了解它的结构是阐明它的功能和代谢影响的关键.
研究的目的:
- 确定人类甜味受体的三维结构.
- 阐明糖和甜味剂的结合机制.
- 了解受体的激活和信号传导途径.
主要方法:
- 电子显微镜 (cryo-EM) 以获得高分辨率的结构.
- 对蛋白质功能的研究进行变异性研究.
- 分子动力学模拟来分析连接物相互作用.
主要成果:
- 呈现了全长的人类甜味受体在apo和糖结合状态中的结构.
- 揭示了一个不对称的异构体结构与糖结合TAS1R2的金星域.
- 界定了甜味剂识别模式,并确定了结合器结合时的形状变化.
结论:
- 这项研究提供了人类甜味受体综合体的第一个结构性见解.
- 确定了一个独特的激活机制和甜味剂结合的分子基础.
- 提供了设计具有定制性质的新型甜味剂的基础.
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