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研究揭示呼吸系统复合物I的一种普遍耦合机制
2022-09-18 16:47

奥地利科学技术研究所Leonid Sazanov研究组揭示呼吸系统复合物I的一种普遍耦合机制。这一研究成果于2022年9月14日在线发表在国际学术期刊《自然》上。

研究人员报道了大肠杆菌复合体I(EcCI)在不同氧化还原状态下的冷冻电镜结构,包括催化周转。EcCI主要以开放状态存在,其中醌腔暴露在细胞膜上,允许水分子进入,从而使醌移动。与哺乳动物的类似物不同,EcCI只有在周转过程中才能转换为封闭状态,这表明封闭状态和开放状态是真正的周转中间体。开放到闭合的转变导致紧密吞噬的醌腔与膜臂的中轴相连,这是底物质子的来源。一致的是,封闭状态的比例随着pH值的增加而增加。研究人员提出了一个详细但直接和稳健的机制,包括质子转移和静电相互作用的"多米诺骨牌效应"串联:正向波("多米诺骨牌堆叠")为泵提供动力,反向波("多米诺骨牌倒下")导致所有泵出的质子从远端亚单位NuoL排出。这一机制解释了为什么质子只从NuoL亚单位排出,并得到诱变数据的支持。研究人员认为,这是复合体I和相关酶的一种普遍的耦合机制。

据了解,复合物I是呼吸链中的第一个酶,负责线粒体和细菌的能量生产。复合物I将两个电子从NADH转移到醌,并将四个质子转运到膜上,但其耦合机制仍有争议。

附:英文原文

Title: A universal coupling mechanism of respiratory complex I

Author: Kravchuk, Vladyslav, Petrova, Olga, Kampjut, Domen, Wojciechowska-Bason, Anna, Breese, Zara, Sazanov, Leonid

Issue&Volume: 2022-09-14

Abstract: Complex I is the first enzyme in the respiratory chain, which is responsible for energy production in mitochondria and bacteria1. Complex I couples the transfer of two electrons from NADH to quinone and the translocation of four protons across the membrane2, but the coupling mechanism remains contentious. Here we present cryo-electron microscopy structures of Escherichia coli complex I (EcCI) in different redox states, including catalytic turnover. EcCI exists mostly in the open state, in which the quinone cavity is exposed to the cytosol, allowing access for water molecules, which enable quinone movements. Unlike the mammalian paralogues3, EcCI can convert to the closed state only during turnover, showing that closed and open states are genuine turnover intermediates. The open-to-closed transition results in the tightly engulfed quinone cavity being connected to the central axis of the membrane arm, a source of substrate protons. Consistently, the proportion of the closed state increases with increasing pH. We propose a detailed but straightforward and robust mechanism comprising a ‘domino effect’ series of proton transfers and electrostatic interactions: the forward wave (‘dominoes stacking’) primes the pump, and the reverse wave (‘dominoes falling’) results in the ejection of all pumped protons from the distal subunit NuoL. This mechanism explains why protons exit exclusively from the NuoL subunit and is supported by our mutagenesis data. We contend that this is a universal coupling mechanism of complex I and related enzymes.

DOI: 10.1038/s41586-022-05199-7

Source: https://www.nature.com/articles/s41586-022-05199-7

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:69.504
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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