DNP和 purin 核酸与 UCP1 的结合的结构基础
Yunlu Kang1, Lei Chen2,3,4,5
1State Key Laboratory of Membrane Biology, College of Future Technology, Institute of Molecular Medicine, Peking University, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Beijing, China.
Nature
|June 19, 2023
概括
解蛋白1 (UCP1) 通过通过内部线粒体膜传导质子来促进热的产生. 结构研究揭示了脂肪酸和核酸如何与UCP1结合,解释了其激活和抑制机制.
科学领域:
- 线粒体生物学
- 结构生物学
- 生物化学
背景情况:
- 解蛋白1 (UCP1) 对于热生成至关重要,它从ATP合成中解呼吸.
- 脂肪酸和精氨酸核酸调节UCP1的活动,但结合机制尚不清楚.
研究的目的:
- 阐明与人类UCP1结合的分子机制.
- 确定脂肪酸激活UCP1和ATP抑制的结构基础.
主要方法:
- 使用X射线结晶学来确定人类UCP1的结构.
- 获得了UCP1无核酸,DNP结合和ATP结合状态的结构.
主要成果:
- 人类UCP1具有从细胞质可访问的开放中央腔.
- 2,4-丁烯醇 (DNP) 与TM2和TM6跨膜螺旋体结合.
- ATP与DNP结合在同一个位置,诱导构造变化并抑制质子运输.
结论:
- 通过占据UCP1活性位点,ATP可以竞争性地抑制DNP结合.
- 结构洞察力解释了UCP1的脂肪酸和核酸的调节.
- 这为了解UCP1在代谢调节中的作用提供了基础.
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