The coupling mechanism of mammalian respiratory complex I
The coupling mechanism of mammalian respiratory complex I
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DOI：
10.1126/science.abc4209
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发表时间：
2020-10-30
期刊：
影响因子：
56.9
通讯作者：
Sazanov, Leonid A.
中科院分区：
文献类型：
--
作者：
Kampjut, Domen;Sazanov, Leonid A.
线粒体复合物I通过一种未知的机制将NADH：泛醌氧化还原偶联到质子泵。在这里，我们提出了绵羊复合物I在五个不同的条件下，包括营业额，在分辨率高达2.3至2.5埃的冷冻电子显微镜结构。分解的水分子使我们能够通过实验确定质子易位途径。醌在沿着醌腔的三个位置结合，抑制剂鱼藤酮也结合在亚基ND 4内。醌腔周围剧烈的构象变化将氧化还原反应与酶的开-闭状态转变过程中的质子易位偶联。在诱导失活状态下，开放构象被ND 6亚基阻止。我们提出了一个详细的分子偶联机制的复合物I，这是一个意想不到的组合的构象变化和静电相互作用。
Mitochondrial complex I couples NADH:ubiquinone oxidoreduction to proton pumping by an unknown mechanism. Here, we present cryo-electron microscopy structures of ovine complex I in five different conditions, including turnover, at resolutions up to 2.3 to 2.5 angstroms. Resolved water molecules allowed us to experimentally define the proton translocation pathways. Quinone binds at three positions along the quinone cavity, as does the inhibitor rotenone that also binds within subunit ND4. Dramatic conformational changes around the quinone cavity couple the redox reaction to proton translocation during open-to-closed state transitions of the enzyme. In the induced deactive state, the open conformation is arrested by the ND6 subunit. We propose a detailed molecular coupling mechanism of complex I, which is an unexpected combination of conformational changes and electrostatic interactions.