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胆固醇和细胞内品味剂激活苦味受体

Yoojoong Kim¹, Ryan H Gumpper¹, Yongfeng Liu¹

¹Department of Pharmacology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

|April 10, 2024

概括

像TAS2R14这样的苦味受体与各种化学物质结合. 新的结构揭示了胆固醇作为激动剂和苦味化合物作为质调节剂,解释了复杂的苦味信号.

科学领域:

结构生物学
分子药理学
G蛋白结合受体

背景情况:

苦味感知涉及2型味觉受体 (TAS2Rs),一种与G蛋白结合的受体.
TAS2R14在口外组织中表达很高,对许多不同的品味物有反应.
TAS2R14广泛的化学识别和信号传递背后的分子机制尚不清楚.

研究的目的:

阐明TAS2R14连体识别和激活的结构基础.
研究胆固醇和特定苦味剂在TAS2R14信号传递中的作用.
了解TAS2R14及其相关G蛋白 (G_gust和G_i1) 之间的相互作用.

主要方法:

用冷电子显微镜 (cryo-EM) 来确定TAS2R14复合物的结构.
计算和生化研究以验证配体与受体的相互作用.
功能分析以评估激动剂和异质调节剂的活性.

主要成果:

两个冷EM结构显示了TAS2R14与G_gust和G_i1复合.
胆固醇被确定为一个正经激素,占据主要的结合口袋.
苦味剂cmpd28.1作为一个积极的全调节剂和直接的激动剂,与细胞内部位结合.
一个延长的腔连接了正和异位,具有疏水的核心.

结论:

结构和功能数据显示了TAS2R14激活的双联体结合点和机制.
胆固醇和cmpd28. 1在调节TAS2R14活性方面发挥着不同的作用.
研究结果表明,TAS2R14的功能超出了味觉感知,涉及细胞内全质调节.

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