糖皮质体结合的粘附受体GPR97-Go复合物的结构
Yu-Qi Ping1,2,3, Chunyou Mao4,5, Peng Xiao3
1CAS Key Laboratory of Receptor Research, Center for Structure and Function of Drug Targets, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
葡萄糖皮质激素激活粘附G蛋白结合受体G3 (ADGRG3). 结构研究揭示了这些激素如何结合和激活ADGRG3,为GPCR调节提供了洞察力.
科学领域:
- 结构生物学
- 生物化学
- 药理学
背景情况:
- 粘附G蛋白合受体 (GPCRs) 是一个重要的GPCR家族,对其连接体调节和结构的理解有限.
- 粘附G蛋白合受体G3 (ADGRG3),也称为GPR97,是该家族的原型成员.
研究的目的:
- 研究ADGRG3的配体调节和激活的结构基础.
- 阐明葡萄皮质激素与ADGRG3相互作用并激活的机制.
主要方法:
- 使用冷电子显微镜确定GPR97-Go复合物的结构.
- 研究的复合物分别与抗炎药物和类固醇激素结合.
主要成果:
- 发现葡萄皮质类药物与跨膜域口袋结合,与"切换开关"残留物W6. 53相互作用以诱导受体激活.
- 活跃的GPR97使用四元核和HLY动机来稳定七个跨膜束和G蛋白合.
- 鉴定出Go蛋白的细胞质尾部的棕化对于有效的GPR97参与至关重要,这是其他GPCR复合体中未见的特征.
结论:
- 这项研究提供了对粘附GPCR的跨膜域内的第一个结构洞察.
- 这些发现为了解ADGRG3的葡萄皮质激活和随后的G蛋白信号提供了结构框架.
- 在ADGRG3激活中Go蛋白棕化具有独特的作用,突出了GPCR- G蛋白相互作用的新方面.
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