气候变化领域集成服务门户(CCPortal): Deactivation blocks proton pathways in the mitochondrial complex I

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DOI	10.1073/pnas.2019498118
	Deactivation blocks proton pathways in the mitochondrial complex I
	Röpke M.; Riepl D.; Saura P.; Luca A.D.; Mühlbauer M.E.; Jussupow A.; Gamiz-Hernandez A.P.; Kaila V.R.I.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:29
英文摘要	Cellular respiration is powered by membrane-bound redox enzymes that convert chemical energy into an electrochemical proton gradient and drive the energy metabolism. By combining large-scale classical and quantum mechanical simulations with cryo-electron microscopy data, we resolve here molecular details of conformational changes linked to proton pumping in the mammalian complex I. Our data suggest that complex I deactivation blocks water-mediated proton transfer between a membrane-bound quinone site and proton-pumping modules, decoupling the energy-transduction machinery. We identify a putative gating region at the interface between membrane domain subunits ND1 and ND3/ND4L/ND6 that modulates the proton transfer by conformational changes in transmembrane helices and bulky residues. The region is perturbed by mutations linked to human mitochondrial disorders and is suggested to also undergo conformational changes during catalysis of simpler complex I variants that lack the “active”-to-“deactive” transition. Our findings suggest that conformational changes in transmembrane helices modulate the proton transfer dynamics by wetting/dewetting transitions and provide important functional insight into the mammalian respiratory complex I. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Cell respiration \| bioenergetics \| molecular simulations \| QM/MM \| cryoEM
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/238471
作者单位	Department Chemie, Technische Universität München, Garching, D-85747, Germany; Department of Biochemistry and Biophysics, Stockholm University, Stockholm, 10691, Sweden
推荐引用方式 GB/T 7714	Röpke M.,Riepl D.,Saura P.,et al. Deactivation blocks proton pathways in the mitochondrial complex I[J],2021,118(29).
APA	Röpke M..,Riepl D..,Saura P..,Luca A.D..,Mühlbauer M.E..,...&Kaila V.R.I..(2021).Deactivation blocks proton pathways in the mitochondrial complex I.Proceedings of the National Academy of Sciences of the United States of America,118(29).
MLA	Röpke M.,et al."Deactivation blocks proton pathways in the mitochondrial complex I".Proceedings of the National Academy of Sciences of the United States of America 118.29(2021).