通过葡萄糖输送器识别和运输的分子基础
Dong Deng1,2,3, Pengcheng Sun1,2,3, Chuangye Yan1,2,3
1State Key Laboratory of Membrane Biology, Tsinghua University, Beijing 100084, China.
Nature
|July 16, 2015
概括
研究人员确定了与葡萄糖和麦芽糖结合的人类葡萄糖转运体3 (GLUT3) 的高分辨率结构. 这揭示了传送器的关键洞察力.
科学领域:
- 生物化学
- 结构生物学
- 膜运输
背景情况:
- 像人类GLUT1-4一样,主要促进物超级家族 (MFS) 的葡萄糖运输体对于溶液运输至关重要.
- 了解它们的结构和机制对于代谢研究至关重要.
研究的目的:
- 阐明人类GLUT3与D-葡萄糖复合的高分辨率结构.
- 通过结构分析研究GLUT3的构造状态和连接.
主要方法:
- 脂质立方相结晶
- 微焦的X射线衍射.
- 在高分辨率 (1.5 Å,2.6 Å,2.4 Å) 上确定三个不同的GLUT3结构.
主要成果:
- 在1.5 Å分辨率下以外向遮蔽状态确定人类GLUT3的结构.
- 在向外开放和向外遮蔽状态下获得GLUT3的结构.
- 确定了碳酸终端域中的极性残留物作为主要连接物协调物.
- 在形状变化期间观察到跨膜段TM7的关键重新排列.
结论:
- 在GLUT中,C端域是主要的基质结合部位.
- 通过对GLUT3和GLUT1结构进行比较,可以了解GLUT的交替访问机制.
- 为GLUT提供了机制理解和结构导向的连接体设计的框架.
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