哺乳动物果糖转运体GLUT5的结构和机制
Norimichi Nomura1,2,3, Grégory Verdon4,5,6, Hae Joo Kang4,5,6
1Department of Cell Biology, Graduate School of Medicine, Kyoto University, Konoe-cho, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan.
Nature
|September 30, 2015
概括
果糖转运体GLUT5活动的改变与糖尿病和肥胖有关. 结构分析显示一个封闭孔机制和一个单一的突变切换GLUT5
科学领域:
- 生物化学
- 结构生物学
- 分子生物学
背景情况:
- 改变果糖运输体GLUT5的活性与2型糖尿病,肥胖和某些癌症有关.
- GLUT5 是一个关键的单糖转运体,具有作为药物标的潜力.
研究的目的:
- 阐明GLUT5功能和基板运输的结构基础.
- 研究GLUT5中的单糖转移机制.
主要方法:
- 确定Rattus norvegicus GLUT5 (面向外) 和Bos taurus GLUT5 (面向内) 的晶体结构.
- 将GLUT5结构与人类GLUT1和大肠杆菌XylE进行比较,以了解传输机制.
- 使用结构比较来确定基质特异性的关键残留物.
主要成果:
- 解析了GLUT5结构的明显开放形状,揭示了主要的促进器超级家族折叠.
- 证明单点突变可以改变GLUT5从果糖到葡萄糖的基质偏好.
- 提出了一个"孔"传输机制,涉及TM7和TM10跨膜束中的螺旋重排.
结论:
- 对GLUT5的结构洞察力为了解其在代谢障碍中的作用提供了基础.
- 发现的"孔"机制为单糖转运器功能提供了新的视角.
- 这些发现为设计针对GLUT5相关疾病的向抑制剂铺平了道路.
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