黑受体的胆固醇运输类活动的结构基础
Yunxiao Zhang1, David P Bulkley2, Yao Xin3
1Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94158, USA.
Cell
|November 13, 2018
概括
补丁 (PTCH1) 蛋白通过控制胆固醇的可用性来调节平滑的活性,影响鼠信号传递和基底细胞癌的发展. 这表明PTCH1在胆固醇运输中的新角色.
科学领域:
- 分子生物学
- 细胞信号传输
- 结构生物学
背景情况:
- 刺 (Hh) 蛋白对于组织的发育和维护至关重要.
- 补丁 (PTCH1) 是一种12个跨膜受体,抑制了Hh通路的关键组成部分SMO.
- PTCH1功能的丧失与基底细胞癌 (BCC) 有关.
研究的目的:
- 阐明PTCH1功能的结构基础.
- 研究PTCH1,SMO和胆固醇之间的关系.
- 了解PTCH1在Hh通路调节中的作用.
主要方法:
- 用冷电子显微镜 (cryo-EM) 来确定PTCH1的结构.
- 对RND传送器的跨膜域相似性的分析.
- 对PTCH1和Hh刺激反应中的胆固醇活性的研究.
主要成果:
- PTCH1与 Prokaryotic RND 载体具有结构上的相似性,具有疏水导管.
- 这条管道含有类似胆固醇的分子,
- 通过Hh信号恢复的PTCH1表达降低了血膜胆固醇.
结论:
- PTCH1可能充当胆固醇转运体.
- 通过调节血膜中的胆固醇可用性,PTCH1调节SMO活性.
- 这种机制为Hh通路调节和BCC病变提供了新的见解.
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