登録情報 データベース : EMDB / ID : EMD-16518 ダウンロードとリンクタイトル Cryo-EM structure NDUFS4 knockout complex I from Mus musculus heart (Class 3). マップデータglobally sharpened map 詳細 試料複合体 : Very long-chain specific acyl-CoA dehydrogenase, mitochondrialリガンド : x 11種 詳細 キーワード NADH ubiquinone oxidoreductase / Complex I / OXIDOREDUCTASE機能・相同性 機能・相同性情報分子機能 ドメイン・相同性 構成要素
Mitochondrial protein import / Protein lipoylation / Mitochondrial Fatty Acid Beta-Oxidation / Complex I biogenesis / RHOG GTPase cycle / Respiratory electron transport / protein insertion into mitochondrial inner membrane / blastocyst hatching / ubiquinone-6 biosynthetic process / Mitochondrial protein degradation ... Mitochondrial protein import / Protein lipoylation / Mitochondrial Fatty Acid Beta-Oxidation / Complex I biogenesis / RHOG GTPase cycle / Respiratory electron transport / protein insertion into mitochondrial inner membrane / blastocyst hatching / ubiquinone-6 biosynthetic process / Mitochondrial protein degradation / response to light intensity / cellular response to oxygen levels / iron-sulfur cluster assembly complex / : / mitochondrial large ribosomal subunit binding / negative regulation of insulin secretion involved in cellular response to glucose stimulus / gliogenesis / negative regulation of non-canonical NF-kappaB signal transduction / cellular response to glucocorticoid stimulus / neural precursor cell proliferation / cardiac muscle tissue development / [2Fe-2S] cluster assembly / oxygen sensor activity / positive regulation of mitochondrial membrane potential / response to hydroperoxide / : / ubiquinone binding / iron-sulfur cluster assembly / positive regulation of ATP biosynthetic process / NADH:ubiquinone reductase (H+-translocating) / positive regulation of execution phase of apoptosis / proton motive force-driven mitochondrial ATP synthesis / NADH dehydrogenase activity / apoptotic mitochondrial changes / mitochondrial ATP synthesis coupled electron transport / respiratory chain complex I / : / mitochondrial electron transport, NADH to ubiquinone / mitochondrial respiratory chain complex I assembly / electron transport coupled proton transport / acyl binding / acyl carrier activity / NADH dehydrogenase (ubiquinone) activity / cellular response to interferon-beta / negative regulation of intrinsic apoptotic signaling pathway / ATP synthesis coupled electron transport / quinone binding / cellular response to retinoic acid / negative regulation of reactive oxygen species biosynthetic process / extrinsic apoptotic signaling pathway / ionotropic glutamate receptor binding / Neutrophil degranulation / aerobic respiration / response to hormone / neurogenesis / respiratory electron transport chain / cerebellum development / reactive oxygen species metabolic process / regulation of mitochondrial membrane potential / response to cocaine / synaptic membrane / response to nicotine / mitochondrial membrane / electron transport chain / response to hydrogen peroxide / negative regulation of cell growth / response to organic cyclic compound / mitochondrial intermembrane space / 2 iron, 2 sulfur cluster binding / circadian rhythm / positive regulation of protein catabolic process / NAD binding / FMN binding / myelin sheath / nervous system development / 4 iron, 4 sulfur cluster binding / protease binding / in utero embryonic development / response to ethanol / response to oxidative stress / mitochondrial inner membrane / electron transfer activity / nuclear body / response to hypoxia / nuclear speck / mitochondrial matrix / response to xenobiotic stimulus / negative regulation of DNA-templated transcription / neuronal cell body / dendrite / ubiquitin protein ligase binding / synapse / protein-containing complex binding / protein kinase binding / endoplasmic reticulum / protein-containing complex / mitochondrion / nucleoplasm / ATP binding / membrane 類似検索 - 分子機能 : / NmrA-like domain / NmrA-like family / Complex1_LYR-like / NADH:ubiquinone oxidoreductase, subunit NDUFB4 / : / NADH-ubiquinone oxidoreductase 1 subunit C1 / NADH dehydrogenase [ubiquinone] 1 subunit C1, mitochondrial / NADH:ubiquinone oxidoreductase, ESSS subunit / ESSS subunit of NADH:ubiquinone oxidoreductase (complex I) ... : / NmrA-like domain / NmrA-like family / Complex1_LYR-like / NADH:ubiquinone oxidoreductase, subunit NDUFB4 / : / NADH-ubiquinone oxidoreductase 1 subunit C1 / NADH dehydrogenase [ubiquinone] 1 subunit C1, mitochondrial / NADH:ubiquinone oxidoreductase, ESSS subunit / ESSS subunit of NADH:ubiquinone oxidoreductase (complex I) / NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 1, NDUB1 / MNLL subunit / NADH-ubiquinone oxidoreductase B15 subunit (NDUFB4) / NADH-ubiquinone oxidoreductase flavoprotein 3 / NADH dehydrogenase [ubiquinone] flavoprotein 3, mitochondrial / Tim17/Tim22/Tim23/Pmp24 family / NADH-ubiquinone oxidoreductase, subunit 10 / NADH-ubiquinone oxidoreductase subunit 10 / NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 10 / NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 8, metazoa / NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 2, animal type / NADH dehydrogenase 1 beta subcomplex subunit 2 / NADH dehydrogenase [ubiquinone] 1 subunit C2, NDUC2 / NADH-ubiquinone oxidoreductase subunit b14.5b (NDUFC2) / NADH dehydrogenase 1, beta subcomplex, subunit 6 / NADH:ubiquinone oxidoreductase, NDUFB6/B17 subunit / : / NADH:ubiquinone oxidoreductase chain 4, N-terminal / NADH:ubiquinone oxidoreductase, chain 2 / NADH dehydrogenase subunit 2, C-terminal / NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 10, mitochondrial / NADH:ubiquinone oxidoreductase, NDUFB5/SGDH subunit / : / NADH-ubiquinone oxidoreductase chain 4, amino terminus / NADH dehydrogenase subunit 2 C-terminus / NADH:ubiquinone oxidoreductase, NDUFB5/SGDH subunit / : / NADH dehydrogenase [ubiquinone] (complex I), alpha subcomplex subunit 1 / NADH-ubiquinone oxidoreductase MWFE subunit / NADH-ubiquinone oxidoreductase NDSU1/NuoG-like, 4Fe-4S domain / NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 8 / NADH-ubiquinone oxidoreductase ASHI subunit (CI-ASHI or NDUFB8) / NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 7 / NADH:ubiquinone oxidoreductase subunit B14.5a (Complex I-B14.5a) / NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 3 / NADH dehydrogenase 1 alpha subcomplex subunit 3 / NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 11 / NADH dehydrogenase subunit 5, C-terminal / NADH dehydrogenase subunit 5 C-terminus / NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 3 / NADH-ubiquinone oxidoreductase B12 subunit family / NADH:ubiquinone oxidoreductase, NDUFS5-15kDa / NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 7, NDUB7 / NADH-ubiquinone oxidoreductase B18 subunit (NDUFB7) / GRIM-19 / GRIM-19 protein / NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 9 / NDUFB9, LYR domain / NADH:ubiquinone oxidoreductase, iron-sulphur subunit 5 / NADH-ubiquinone/plastoquinone oxidoreductase chain 6, subunit NuoJ / NADH:ubiquinone/plastoquinone oxidoreductase, chain 6 / NDUFA6, LYR domain / NADH dehydrogenase [ubiquinone] (complex I), alpha subcomplex, subunit 2 / Deoxynucleoside kinase domain / Deoxynucleoside kinase / NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 5 / ETC complex I subunit conserved region / NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 12 / NADH ubiquinone oxidoreductase subunit NDUFA12 / NADH dehydrogenase [ubiquinone] (complex I), alpha subcomplex, subunit 6 / NADH-quinone oxidoreductase, chain G, C-terminal / : / NADH-ubiquinone oxidoreductase subunit G, C-terminal / NADH-quinone oxidoreductase subunit 3, ferredoxin-like domain / SLBB domain / : / NADH dehydrogenase [ubiquinone] (complex I), alpha subcomplex, subunit 8 / NADH-ubiquinone/plastoquinone oxidoreductase chain 6 / Respiratory-chain NADH dehydrogenase 20 Kd subunit signature. / NADH-ubiquinone oxidoreductase, 20 Kd subunit / NADH-quinone oxidoreductase, chain I / NADH-plastoquinone oxidoreductase, chain 5 subgroup / NADH-quinone oxidoreductase, chain M/4 / NADH-ubiquinone oxidoreductase chain 4L/K / Complex 1 LYR protein domain / NADH-Ubiquinone oxidoreductase (complex I), chain 5 N-terminal / NADH-Ubiquinone oxidoreductase (complex I), chain 5 N-terminus / Complex 1 protein (LYR family) / NAD(P)H-quinone oxidoreductase subunit D/H / NADH-quinone oxidoreductase, chain 5-like / NADH:ubiquinone oxidoreductase, 49kDa subunit, conserved site / NADH-ubiquinone oxidoreductase chain 4L/Mnh complex subunit C1-like / NADH-ubiquinone/plastoquinone oxidoreductase chain 4L / Respiratory chain NADH dehydrogenase 49 Kd subunit signature. / : / NADH-quinone oxidoreductase, subunit D / NADH:ubiquinone oxidoreductase, subunit G / Respiratory-chain NADH dehydrogenase, 49 Kd subunit / Respiratory-chain NADH dehydrogenase 75 Kd subunit signature 3. / Respiratory-chain NADH dehydrogenase 75 Kd subunit signature 2. 類似検索 - ドメイン・相同性 NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 11 / NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 11, mitochondrial / NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 1 / NADH-ubiquinone oxidoreductase chain 1 / NADH-ubiquinone oxidoreductase chain 2 / NADH-ubiquinone oxidoreductase chain 3 / NADH-ubiquinone oxidoreductase chain 4L / NADH-ubiquinone oxidoreductase chain 4 / NADH-ubiquinone oxidoreductase chain 5 / NADH-ubiquinone oxidoreductase chain 6 ... NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 11 / NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 11, mitochondrial / NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 1 / NADH-ubiquinone oxidoreductase chain 1 / NADH-ubiquinone oxidoreductase chain 2 / NADH-ubiquinone oxidoreductase chain 3 / NADH-ubiquinone oxidoreductase chain 4L / NADH-ubiquinone oxidoreductase chain 4 / NADH-ubiquinone oxidoreductase chain 5 / NADH-ubiquinone oxidoreductase chain 6 / NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 1 / NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 6 / NADH dehydrogenase [ubiquinone] 1 alpha subcomplex assembly factor 2 / NADH dehydrogenase [ubiquinone] flavoprotein 3, mitochondrial / NADH dehydrogenase [ubiquinone] iron-sulfur protein 8, mitochondrial / NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial / NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial / NADH dehydrogenase [ubiquinone] flavoprotein 1, mitochondrial / NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 10, mitochondrial / NADH dehydrogenase [ubiquinone] iron-sulfur protein 5 / NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 5 / NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 2, mitochondrial / NADH dehydrogenase [ubiquinone] 1 subunit C2 / NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 2 / NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 3 / NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 4 / NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 5, mitochondrial / NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 9 / NADH dehydrogenase [ubiquinone] 1 subunit C1, mitochondrial / NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 6 / NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 3 / Acyl carrier protein, mitochondrial / NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 7 / NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 8, mitochondrial / NADH dehydrogenase [ubiquinone] flavoprotein 2, mitochondrial / NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 9, mitochondrial / NADH dehydrogenase [ubiquinone] iron-sulfur protein 7, mitochondrial / NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 8 / NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 10 / NADH dehydrogenase [ubiquinone] iron-sulfur protein 3, mitochondrial / NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 13 / NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 7 類似検索 - 構成要素生物種 Mus musculus (ハツカネズミ)手法 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 3.9 Å 詳細 データ登録者Yin Z / Bridges HR / Agip ANA / Hirst J 資金援助 英国, 3件 詳細 詳細を隠すOrganization Grant number 国 Medical Research Council (MRC, United Kingdom) MC_U105663141 英国 Medical Research Council (MRC, United Kingdom) MC_UU_00015/2 英国 Medical Research Council (MRC, United Kingdom) MC_UU_00028/1 英国
引用ジャーナル : EMBO J / 年 : 2024タイトル : Structural insights into respiratory complex I deficiency and assembly from the mitochondrial disease-related ndufs4 mouse.著者 : Zhan Yin / Ahmed-Noor A Agip / Hannah R Bridges / Judy Hirst / 要旨 : Respiratory complex I (NADH:ubiquinone oxidoreductase) is essential for cellular energy production and NAD homeostasis. Complex I mutations cause neuromuscular, mitochondrial diseases, such as Leigh ... Respiratory complex I (NADH:ubiquinone oxidoreductase) is essential for cellular energy production and NAD homeostasis. Complex I mutations cause neuromuscular, mitochondrial diseases, such as Leigh Syndrome, but their molecular-level consequences remain poorly understood. Here, we use a popular complex I-linked mitochondrial disease model, the ndufs4 mouse, to define the structural, biochemical, and functional consequences of the absence of subunit NDUFS4. Cryo-EM analyses of the complex I from ndufs4 mouse hearts revealed a loose association of the NADH-dehydrogenase module, and discrete classes containing either assembly factor NDUFAF2 or subunit NDUFS6. Subunit NDUFA12, which replaces its paralogue NDUFAF2 in mature complex I, is absent from all classes, compounding the deletion of NDUFS4 and preventing maturation of an NDUFS4-free enzyme. We propose that NDUFAF2 recruits the NADH-dehydrogenase module during assembly of the complex. Taken together, the findings provide new molecular-level understanding of the ndufs4 mouse model and complex I-linked mitochondrial disease. 履歴 登録 2023年1月24日 - ヘッダ(付随情報) 公開 2023年12月20日 - マップ公開 2023年12月20日 - 更新 2024年10月16日 - 現状 2024年10月16日 処理サイト : PDBe / 状態 : 公開
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