人类大麻素受体CB2的晶体结构
Xiaoting Li1, Tian Hua2, Kiran Vemuri3
1iHuman Institute, ShanghaiTech University, Shanghai 201210, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Science, Chinese Academy of Sciences, Shanghai, China; University of the Chinese Academy of Sciences, Beijing 100049, China.
Cell
|January 15, 2019
概括
研究人员阐明了与抗体结合的人类大麻素受体CB2的结构. 这一发现为开发针对各种疾病的向疗法提供了新的途径,
科学领域:
- 结构生物学
- 药理学
- 免疫学
背景情况:
- 大麻素受体CB2主要存在于免疫系统中.
- 选择性CB2调节为炎症性,纤维性和神经退行性疾病提供治疗潜力,避免CB1受体的精神活性.
研究的目的:
- 用对抗剂AM10257确定人类CB2的晶体结构.
- 研究CB2和CB1受体功能和选择性的分子基础.
- 了解CB2受体激活机制的合理药物设计.
主要方法:
- 人类CB2-AM10257复合物的X射线晶体学 (2.8 Å分辨率).
- 突变性研究.
- 进行分子对接模拟.
主要成果:
- 与CB1相比,CB2-AM10257的结构显示出一种独特的结合姿势.
- 在对抗剂结合的CB2和对抗剂结合的CB1之间观察到形状相似性.
- AM10257表现出相反的功能特征:CB2对抗性和CB1对抗性.
- 分子分析揭示了CB2和CB1功能和选择性的基础.
结论:
- 这项研究提供了与抗体复合的人类CB2的晶体结构.
- 这些发现有助于合理设计药物以精确调节内分泌系统.
- 通过对设计的配体对进行分析,可以了解CB2激活机制.
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