Department Chemie, Technische Universität München (TUM), Lichtenbergstraße 4, D-85747 Garching, Germany.
Sci Adv. 2019 Mar 20;5(3):eaav1850. doi: 10.1126/sciadv.aav1850. eCollection 2019 Mar.
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.
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 作为线粒体和细菌呼吸链中的主要氧化还原驱动质子泵，其活性被心磷脂强烈增强。然而，尽管在复合物 I 的结构生物学方面取得了最近的进展，但心磷脂特异性相互作用机制目前仍不清楚。基于毫秒级分子模拟，我们提出心磷脂结合到复合物 I 的质子泵亚基上，并诱导全局构象变化，从而调节醌底物与酶的可及性。我们的研究结果提供了关于复合物 I 动力学和活性之间偶联的关键信息，并表明生物膜如何调节蛋白质的结构和活性。
