登録情報 データベース : EMDB / ID : EMD-11810 構造の表示 ダウンロードとリンクタイトル Cryo-EM structure of respiratory complex I in the deactive state from Mus musculus at 3.2 A マップデータ 詳細 試料複合体 : Mouse mitochondrial complex Iリガンド : x 10種 詳細 キーワード deactive 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 / response to injury involved in regulation of muscle adaptation / mesenchymal stem cell proliferation / reproductive system development / Protein lipoylation / Mitochondrial Fatty Acid Beta-Oxidation / Complex I biogenesis / RHOG GTPase cycle / Respiratory electron transport / protein insertion into mitochondrial inner membrane ... Mitochondrial protein import / response to injury involved in regulation of muscle adaptation / mesenchymal stem cell proliferation / reproductive system development / Protein lipoylation / Mitochondrial Fatty Acid Beta-Oxidation / Complex I biogenesis / RHOG GTPase cycle / Respiratory electron transport / protein insertion into mitochondrial inner membrane / mesenchymal stem cell differentiation / circulatory system development / blastocyst hatching / respiratory system process / psychomotor behavior / Mitochondrial protein degradation / cellular response to oxygen levels / stem cell division / respiratory chain complex / response to light intensity / mitochondrial [2Fe-2S] assembly complex / iron-sulfur cluster assembly complex / mitochondrial large ribosomal subunit binding / gliogenesis / negative regulation of non-canonical NF-kappaB signal transduction / cardiac muscle tissue development / neural precursor cell proliferation / positive regulation of mitochondrial membrane potential / [2Fe-2S] cluster assembly / adult walking behavior / cellular response to glucocorticoid stimulus / oxygen sensor activity / response to hydroperoxide / iron-sulfur cluster assembly / positive regulation of ATP biosynthetic process / dopamine metabolic process / adult behavior / NADH:ubiquinone reductase (H+-translocating) / mitochondrial respiratory chain complex I assembly / positive regulation of execution phase of apoptosis / mitochondrial electron transport, NADH to ubiquinone / NADH dehydrogenase activity / proton motive force-driven mitochondrial ATP synthesis / respiratory chain complex I / NADH dehydrogenase (ubiquinone) activity / neuron development / quinone binding / cellular response to interferon-beta / ATP synthesis coupled electron transport / cellular response to retinoic acid / negative regulation of reactive oxygen species biosynthetic process / extrinsic apoptotic signaling pathway / neurogenesis / tricarboxylic acid cycle / muscle contraction / Neutrophil degranulation / visual perception / cerebellum development / reactive oxygen species metabolic process / aerobic respiration / DNA damage response, signal transduction by p53 class mediator / regulation of mitochondrial membrane potential / kidney development / fatty acid metabolic process / respiratory electron transport chain / mitochondrion organization / response to nicotine / sensory perception of sound / response to cocaine / monooxygenase activity / electron transport chain / mitochondrial membrane / : / brain development / multicellular organism growth / response to hydrogen peroxide / mitochondrial intermembrane space / 2 iron, 2 sulfur cluster binding / cognition / circadian rhythm / positive regulation of protein catabolic process / NAD binding / fatty acid biosynthetic process / cellular senescence / FMN binding / nervous system development / myelin sheath / 4 iron, 4 sulfur cluster binding / neuron apoptotic process / gene expression / response to oxidative stress / in utero embryonic development / response to ethanol / response to hypoxia / electron transfer activity / mitochondrial inner membrane / nuclear speck / nuclear body / mitochondrial matrix / inflammatory response 類似検索 - 分子機能 NmrA-like domain / NmrA-like family / Complex1_LYR-like / 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 flavoprotein 3 ... NmrA-like domain / NmrA-like family / Complex1_LYR-like / 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 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] iron-sulfur protein 6, mitochondrial / 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 NDUFB4 / NADH-ubiquinone oxidoreductase subunit b14.5b (NDUFC2) / NADH-ubiquinone oxidoreductase B15 subunit (NDUFB4) / 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 dehydrogenase [ubiquinone] 1 beta subcomplex subunit 8 / NADH-ubiquinone oxidoreductase ASHI subunit (CI-ASHI or NDUFB8) / NADH-ubiquinone oxidoreductase NDSU1/NuoG-like, 4Fe-4S domain / 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 / Zinc finger, CHCC-type / Zinc-finger domain / 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 / NDUFA6, LYR domain / Deoxynucleoside kinase domain / Deoxynucleoside kinase / NADH dehydrogenase ubiquinone Fe-S protein 4-like superfamily / NADH dehydrogenase ubiquinone Fe-S protein 4 / NADH dehydrogenase [ubiquinone] (complex I), alpha subcomplex, subunit 2 / NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 5 / NADH dehydrogenase ubiquinone Fe-S protein 4, mitochondrial / 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 / : / SLBB domain / NADH dehydrogenase [ubiquinone] (complex I), alpha subcomplex, subunit 8 / : / : / NADH-quinone oxidoreductase subunit 3, ferredoxin-like domain / 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-ubiquinone/plastoquinone oxidoreductase chain 6, subunit NuoJ / NADH-quinone oxidoreductase, chain M/4 / NADH-ubiquinone oxidoreductase chain 4L/K / NADH:ubiquinone/plastoquinone oxidoreductase, chain 6 / NADH-ubiquinone/plastoquinone oxidoreductase chain 6 / NADH-Ubiquinone oxidoreductase (complex I), chain 5 N-terminal / NADH-Ubiquinone oxidoreductase (complex I), chain 5 N-terminus / 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:ubiquinone oxidoreductase, subunit G / Respiratory-chain NADH dehydrogenase 75 Kd subunit signature 3. 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] iron-sulfur protein 6, mitochondrial / NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 6 / NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 12 / 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] iron-sulfur protein 4, mitochondrial / 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 : 3.17 Å 詳細 データ登録者Yin Z / Bridges HR 資金援助 英国, 2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
引用ジャーナル : Nat Commun / 年 : 2021タイトル : Structural basis for a complex I mutation that blocks pathological ROS production.著者: Zhan Yin / Nils Burger / Duvaraka Kula-Alwar / Dunja Aksentijević / Hannah R Bridges / Hiran A Prag / Daniel N Grba / Carlo Viscomi / Andrew M James / Amin Mottahedin / Thomas Krieg / ... 著者 : Zhan Yin / Nils Burger / Duvaraka Kula-Alwar / Dunja Aksentijević / Hannah R Bridges / Hiran A Prag / Daniel N Grba / Carlo Viscomi / Andrew M James / Amin Mottahedin / Thomas Krieg / Michael P Murphy / Judy Hirst / 要旨 : Mitochondrial complex I is central to the pathological reactive oxygen species (ROS) production that underlies cardiac ischemia-reperfusion (IR) injury. ND6-P25L mice are homoplasmic for a disease- ... Mitochondrial complex I is central to the pathological reactive oxygen species (ROS) production that underlies cardiac ischemia-reperfusion (IR) injury. ND6-P25L mice are homoplasmic for a disease-causing mtDNA point mutation encoding the P25L substitution in the ND6 subunit of complex I. The cryo-EM structure of ND6-P25L complex I revealed subtle structural changes that facilitate rapid conversion to the "deactive" state, usually formed only after prolonged inactivity. Despite its tendency to adopt the "deactive" state, the mutant complex is fully active for NADH oxidation, but cannot generate ROS by reverse electron transfer (RET). ND6-P25L mitochondria function normally, except for their lack of RET ROS production, and ND6-P25L mice are protected against cardiac IR injury in vivo. Thus, this single point mutation in complex I, which does not affect oxidative phosphorylation but renders the complex unable to catalyse RET, demonstrates the pathological role of ROS production by RET during IR injury. 履歴 登録 2020年9月29日 - ヘッダ(付随情報) 公開 2021年2月3日 - マップ公開 2021年2月3日 - 更新 2025年4月9日 - 現状 2025年4月9日 処理サイト : PDBe / 状態 : 公開
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