期刊
NATURE COMMUNICATIONS
卷 11, 期 1, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41467-020-19778-7
关键词
-
资金
- Deutsche Forschungsgemeinschaft [AN 1080/3-1, ZI 552/4-2]
- Academy of Finland [294652]
- University of Helsinki
- Magnus Ehrnrooth Foundation
- Sigrid Juselius Foundation
- CHEMS doctoral school of the University of Helsinki
- Max Planck Society
- Academy of Finland (AKA) [294652, 294652] Funding Source: Academy of Finland (AKA)
Respiratory complex I catalyzes electron transfer from NADH to ubiquinone (Q) coupled to vectorial proton translocation across the inner mitochondrial membrane. Despite recent progress in structure determination of this very large membrane protein complex, the coupling mechanism is a matter of ongoing debate and the function of accessory subunits surrounding the canonical core subunits is essentially unknown. Concerted rearrangements within a cluster of conserved loops of central subunits NDUFS2 (beta 1-beta 2(S2) loop), ND1 (TMH5-6(ND1) loop) and ND3 (TMH1-2(ND3) loop) were suggested to be critical for its proton pumping mechanism. Here, we show that stabilization of the TMH1-2(ND3) loop by accessory subunit LYRM6 (NDUFA6) is pivotal for energy conversion by mitochondrial complex I. We determined the high-resolution structure of inactive mutant F89A(LYRM6) of eukaryotic complex I from the yeast Yarrowia lipolytica and found long-range structural changes affecting the entire loop cluster. In atomistic molecular dynamics simulations of the mutant, we observed conformational transitions in the loop cluster that disrupted a putative pathway for delivery of substrate protons required in Q redox chemistry. Our results elucidate in detail the essential role of accessory subunit LYRM6 for the function of eukaryotic complex I and offer clues on its redox-linked proton pumping mechanism. Respiratory complex I plays a key role in energy metabolism. Cryo-EM structure of a mutant accessory subunit LYRM6 from the yeast Yarrowia lipolytica and molecular dynamics simulations reveal conformational changes at the interface between LYRM6 and subunit ND3, propagated further into the complex. These findings offer insight into the mechanism of proton pumping by respiratory complex I.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据