线粒体复合体I的催化后结构与乌比奎诺-10结合在活性部位
Injae Chung1,2, Caroline S Pereira3, John J Wright1
1MRC Mitochondrial Biology Unit, University of Cambridge, The Keith Peters Building, Cambridge Biomedical Campus, Cambridge, UK.
Nature communications
|March 5, 2026
概括
研究人员使用冷EM揭示了呼吸系统复合物I如何减少ubiquinone-10 (Q10) 并出质子. 这项研究澄清了Q10结合的姿势和这一关键能量代谢酶中的质子转移途径.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 线粒体生物学 线粒体生物学
背景情况:
- 呼吸系统复合体I对于细胞能量代谢至关重要,它将NADH氧化与质子接相结合.
- 在复杂I中理解ubiquinone-10 (Q10) 减少和质子转移机制仍然是一个挑战.
研究的目的:
- 为了阐明由呼吸复合体I.减少乌比基-10 (Q10) 的机制细节.
- 为了可视化复杂I的膜域内的质子转移通路.
主要方法:
- 使用电子冷显微镜 (cryo-EM) 来确定哺乳动物复合体I的高分辨率结构.
- 复合物I被重组成含有外源Q10的脂纳米盘,并通过NADH减少.
- 用分子动力学模拟来研究残留电荷状态和基质结合位置.
主要成果:
- 在封闭状态的Q-结合通道内观察到两种减少的乌比奎农-10 (Q10H2) 构造.
- 通过比较氧化和减少的复杂I结构,提出了一系列用于降低Q10的基质结合姿势.
- 高度水合的结构显示了在整个膜域中几乎连续的质子转移连接.
结论:
- 这项研究提供了关于Q10减少机制和呼吸系统复合体I中的质子转位的原子层次见解.
- 识别的质子转移控制点对于理解复杂I催化和能量转导至关重要.
- 这些发现提升了我们对线粒体能量代谢和相关疾病的知识.
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