人类信号系统的发现:合G蛋白合受体
Simon R Foster1, Alexander S Hauser1, Line Vedel1
1Department of Drug Design and Pharmacology, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark.
Cell
|November 2, 2019
概括
研究人员发现了和G蛋白合受体 (GPCRs) 之间的新联系,扩大了我们对人类信号系统的理解. 这一发现为未来研究它们在健康和疾病中的作用铺平了道路.
科学领域:
- 人体生理和分子信号
- 基因组学和生物信息学
- 药物发现和受体药理学
背景情况:
- 体系统是一个庞大的联体受体相互作用网络,仍然不完全理解,许多和G蛋白结合受体 (GPCR) 缺乏明确的生理作用.
- 超过100个G蛋白结合受体 (GPCR) 和众多具有未知的功能,阻碍了对人类信号通路的全面理解.
研究的目的:
- 系统地将相关与相应的G蛋白结合受体 (GPCR) 结合起来.
- 识别新的体信号系统并扩展已知的-GPCR网络.
- 通过将孤儿GPCR与疾病相关疾病联系起来,发现潜在的治疗点.
主要方法:
- 在313个物种中比较基因组学以确定保存的信号特征.
- 对人类A类GPCR序列和结构的生物信息分析.
- 三个直角的生物化学测试以验证受体配对.
主要成果:
- 成功将17个拟议的内源性配体与五个与遗传,瘤,神经和生殖系统疾病相关的孤儿G蛋白结合受体 (GPCR) 配对.
- 确定了9个具有已知关联体和病理生理相关性的G蛋白结合受体 (GPCR) 的额外.
- 发现的普遍特征表明了额外的潜在体信号系统.
结论:
- 这种综合计算和实验方法显著扩大了已知的人类-GPCR网络.
- 这些发现为阐明新发现的信号系统在人类生理和疾病中的作用提供了基础.
- 开辟了针对以前未被描述的性通路的治疗干预的新途径.
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