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人类罗多普辛与抑制性G蛋白结合的冷EM结构
Yanyong Kang1, Oleg Kuybeda2, Parker W de Waal1
1Center for Cancer and Cell Biology, Innovation and Integration Program, Van Andel Research Institute, Grand Rapids, MI, USA.
Nature
|June 15, 2018
概括
与G蛋白结合的受体通过特定的结构相互作用选择性地结合G蛋白或阿斯特林. 这项研究揭示了激活的罗多普辛如何与抑制性G蛋白 (Gi) 在分子水平上相互作用.
科学领域:
- 分子生物学
- 结构生物学
- 生物化学
背景情况:
- G蛋白结合受体 (GPCR) 是哺乳动物中最大的跨膜受体家族.
- GPCRs通过与G蛋白 (刺激性Gs和抑制性Gi) 和阿雷斯相互作用来调解各种细胞功能.
- GPCR与特定传感器的选择性合的结构基础仍然不清楚.
研究的目的:
- 阐明控制GPCR与G蛋白和阿斯特林的选择性合的结构机制.
- 了解激活的罗多与抑制性G蛋白 (Gi) 如何相互作用.
主要方法:
- 使用冷电子显微镜 (cryo-EM) 来确定高分辨率结构.
- 不同的GPCR- 连接物- 传感器复合体进行了结构比较.
主要成果:
- Giα子单元的C端螺旋与罗多的螺旋8直接相互作用.
- 这种相互作用涉及Giα子单元的螺旋入罗多膜束腔.
- 通过将Gi结合的Rhodopsin与Gs结合的β2-上腺素受体进行比较,获得了结构性见解.
结论:
- 这项研究为了解GPCR对Gs,Gi和逮捕素的选择性提供了结构基础.
- 特定的结构签名要求通过激活的GPCR识别不同的信号合作伙伴.
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