Cryo-EM structures of mitochondrial respiratory complex I from Drosophila melanogaster.
Cryo-EM structures of mitochondrial respiratory complex I from Drosophila melanogaster.
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DOI：
10.7554/elife.84424
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发表时间：
2023-01-09
期刊：
影响因子：
7.7
通讯作者：
Hirst, Judy
中科院分区：
文献类型：
--
作者：
Agip, Ahmed-Noor A.;Chung, Injae;Sanchez-Martinez, Alvaro;Whitworth, Alexander J.;Hirst, Judy
关键词：
呼吸复合物I通过氧化磷酸化为ATP合成提供动力，利用辅酶Q氧化NADH的能量驱动质子穿过能量转导膜。黑腹果蝇是复合体I的候选模式生物，因为其与哺乳动物酶的高度进化保守性、良好开发的遗传工具包以及用于特定细胞类型和组织研究的复杂生理学。在这里，我们从果蝇中分离出复合物I，并确定其结构，揭示了一个43-亚基组装与其45-亚基哺乳动物对应物具有高度的结构同源性，包括一个迄今未知的亚基NDUFA 3的同源物。果蝇酶的主要构象状态是具有完全有序和封闭的泛醌结合位点，但与亚基ND 6的变化有关的全局构象发生了微妙的变化的果蝇型“准备就绪”的活性静息状态。未观察到ND 6-TMH 3的“失活”显著静息状态：在两个次要状态下，泛醌结合位点未改变，但失活型π-凸起存在于ND 6-TMH 3中。我们详细的果蝇复合物I的结构知识提供了一个新的方法来解开复合物I的催化和调节机制的生物能量学和生理学的基础。
Respiratory complex I powers ATP synthesis by oxidative phosphorylation, exploiting the energy from NADH oxidation by ubiquinone to drive protons across an energy-transducing membrane. Drosophila melanogaster is a candidate model organism for complex I due to its high evolutionary conservation with the mammalian enzyme, well-developed genetic toolkit, and complex physiology for studies in specific cell types and tissues. Here, we isolate complex I from Drosophila and determine its structure, revealing a 43-subunit assembly with high structural homology to its 45-subunit mammalian counterpart, including a hitherto unknown homologue to subunit NDUFA3. The major conformational state of the Drosophila enzyme is the mammalian-type 'ready-to-go' active resting state, with a fully ordered and enclosed ubiquinone-binding site, but a subtly altered global conformation related to changes in subunit ND6. The mammalian-type 'deactive' pronounced resting state is not observed: in two minor states, the ubiquinone-binding site is unchanged, but a deactive-type π-bulge is present in ND6-TMH3. Our detailed structural knowledge of Drosophila complex I provides a foundation for new approaches to disentangle mechanisms of complex I catalysis and regulation in bioenergetics and physiology.
DOI：
10.1093/pnasnexus/pgac276
发表时间：
2022-11
期刊：
PNAS NEXUS
影响因子：
--
作者：
Jarman, Owen D.;Hirst, Judy
通讯作者：
Hirst, Judy