哺乳动物呼吸复合物I的偶联机制获解析
作者：小柯机器人 发布时间：2020/9/26 10:16:45
奥地利科技学院Leonid A. Sazanov研究组解析出哺乳动物呼吸复合物I的偶联机制。2020年9月24日，《科学》杂志在线发表了这一研究成果。
研究人员报道了绵羊线粒体复合物I在5种不同条件下的冷冻电镜结构，其分辨率高达2.3-2.5Å。解析出的水分子使研究人员能够实验性地定义质子易位途径。醌在沿醌腔的三个位置结合，抑制剂鱼藤酮也结合在亚基ND4内。在酶的“开放”到“闭合”状态转换期间，醌腔周围的构象发生剧烈变化，使氧化还原反应与质子移位耦合。在诱导的失活状态下，“开放”构象被ND6亚基阻滞。
研究人员提出了一种复杂的复合物I详细分子偶联机制，这是构象变化和静电相互作用的意外组合。
据介绍，线粒体复合体I通过未知机理将NADH:泛醌氧化还原与质子泵浦耦合。
附：英文原文
Title:The coupling mechanism of mammalian respiratory complex I
Author:Domen Kampjut, View ORCID ProfileLeonid A. Sazanov*
Issue&Volume:24 Sep 2020
Abstract: Mitochondrial complex I couples NADH:ubiquinone oxidoreduction to proton pumping by an unknown mechanism. Here we present cryo-EM structures of ovine complex I in five different conditions, including turnover, at resolutions up to 2.3-2.5 Å. 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.
DOI:DOI: 10.1126/science.abc4209
Source: https://science.sciencemag.org/content/early/2020/09/23/science.abc4209
期刊信息
Science：《科学》，创刊于1880年。隶属于美国科学促进会，最新IF：41.037