人类光滑受体与抗瘤剂结合的结构
Chong Wang1, Huixian Wu, Vsevolod Katritch
1Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Nature
|May 3, 2013
概括
人类SMO受体跨膜域的晶体结构揭示了其独特的结构以及对抗剂如何结合. 这提供了对刺路径和潜在的癌症药物开发的洞察力.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 分子药理学分子药理学
背景情况:
- 滑化受体 (SMO) 是一种G蛋白结合受体 (GPCR),对胚胎发育至关重要,并与癌症有关.
- SMO是一种F类GPCR,与A类GPCR不同,其序列相似性有限.
- 它在刺信号通路中的作用涉及GLI转录因子.
研究的目的:
- 为了确定人类SMO受体跨膜域的晶体结构.
- 为了可视化小分子抗剂LY2940680.0的结合部位.
- 了解SMO受体功能和对抗性的结构基础.
主要方法:
- 使用X射线结晶学来获得晶体结构.
- 该结构以2.5 Å分辨率确定.
- 该结构捕获了与LY2940680.0结合的SMO受体跨膜域.
主要成果:
- 阐明了人类SMO受体跨膜域的晶体结构.
- 虽然SMO具有7个跨膜螺旋,但它没有保存的A类GPCR动机.
- 结构显示复杂的细胞外环稳定通过二硫化物键,与LY2940680结合在细胞外端.
结论:
- 该SMO受体具有独特的结构架构,与A类GPCR不同.
- 抗体LY2940680在跨膜域内结合,与细胞外循环相互作用.
- 这些结构信息对于理解刺路径信号和开发向癌症疗法至关重要.
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