How cardiolipin modulates the dynamics of respiratory complex I
How cardiolipin modulates the dynamics of respiratory complex I
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DOI：
10.1126/sciadv.aav1850
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发表时间：
2019-03-01
期刊：
影响因子：
13.6
通讯作者：
Kaila, Ville R., I
中科院分区：
文献类型：
--
作者：
Jussupow, Alexander;Di Luca, Andrea;Kaila, Ville R., I
心磷脂调节催化生物能量转导的膜结合呼吸酶的活性。呼吸复合物I在线粒体和细菌呼吸链中作为主要的氧化还原驱动的质子泵发挥作用，并且其活性被心磷脂强烈增强。然而，尽管最近的进展，在复杂的I，心磷脂特异性相互作用机制的结构生物学目前仍然未知。毫秒级分子模拟的基础上，我们建议，心磷脂结合到复合物I的质子泵亚基，并诱导全局构象变化，调节醌底物的酶的可及性。我们的研究结果提供了关键的信息之间的耦合复杂的I动力学和活动，并建议如何生物膜调节蛋白质的结构和活性。
Cardiolipin modulates the activity of membrane-bound respiratory enzymes that catalyze biological energy transduction. The respiratory complex I functions as the primary redox-driven proton pump in mitochondrial and bacterial respiratory chains, and its activity is strongly enhanced by cardiolipin. However, despite recent advances in the structural biology of complex I, cardiolipin-specific interaction mechanisms currently remain unknown. On the basis of millisecond molecular simulations, we suggest that cardiolipin binds to proton-pumping subunits of complex I and induces global conformational changes that modulate the accessibility of the quinone substrate to the enzyme. Our findings provide key information on the coupling between complex I dynamics and activity and suggest how biological membranes modulate the structure and activity of proteins.