+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-11377 | ||||||||||||
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タイトル | Cryo-EM structure of respiratory complex I in the active state from Mus musculus at 3.1 A | ||||||||||||
マップデータ | |||||||||||||
試料 |
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機能・相同性 | 機能・相同性情報 response to injury involved in regulation of muscle adaptation / Protein lipoylation / Mitochondrial Fatty Acid Beta-Oxidation / Complex I biogenesis / reproductive system development / Mitochondrial protein import / Respiratory electron transport / RHOG GTPase cycle / protein insertion into mitochondrial inner membrane / circulatory system development ...response to injury involved in regulation of muscle adaptation / Protein lipoylation / Mitochondrial Fatty Acid Beta-Oxidation / Complex I biogenesis / reproductive system development / Mitochondrial protein import / Respiratory electron transport / RHOG GTPase cycle / protein insertion into mitochondrial inner membrane / circulatory system development / blastocyst hatching / respiratory system process / psychomotor behavior / Mitochondrial protein degradation / cellular response to oxygen levels / iron-sulfur cluster assembly complex / response to light intensity / mitochondrial large ribosomal subunit binding / gliogenesis / neural precursor cell proliferation / cardiac muscle tissue development / negative regulation of non-canonical NF-kappaB signal transduction / : / [2Fe-2S] cluster assembly / oxygen sensor activity / adult walking behavior / cellular response to glucocorticoid stimulus / ubiquinone-6 biosynthetic process / positive regulation of mitochondrial membrane potential / respiratory chain complex I / response to hydroperoxide / cellular respiration / iron-sulfur cluster assembly / NADH dehydrogenase activity / mitochondrial ribosome / adult behavior / dopamine metabolic process / positive regulation of ATP biosynthetic process / mitochondrial translation / NADH:ubiquinone reductase (H+-translocating) / positive regulation of execution phase of apoptosis / apoptotic mitochondrial changes / acyl binding / ubiquinone binding / acyl carrier activity / cellular response to interferon-beta / neuron development / quinone binding / electron transport coupled proton transport / neurogenesis / ATP synthesis coupled electron transport / negative regulation of intrinsic apoptotic signaling pathway / muscle contraction / negative regulation of reactive oxygen species biosynthetic process / ATP metabolic process / cellular response to retinoic acid / extrinsic apoptotic signaling pathway / mitochondrial ATP synthesis coupled electron transport / tricarboxylic acid cycle / mitochondrial respiratory chain complex I assembly / fatty acid metabolic process / : / visual perception / ionotropic glutamate receptor binding / Neutrophil degranulation / respiratory electron transport chain / reactive oxygen species metabolic process / cerebellum development / response to hormone / regulation of mitochondrial membrane potential / : / mitochondrion organization / mitochondrial electron transport, NADH to ubiquinone / response to cocaine / kidney development / synaptic membrane / proton motive force-driven mitochondrial ATP synthesis / NADH dehydrogenase (ubiquinone) activity / apoptotic signaling pathway / electron transport chain / sensory perception of sound / regulation of protein phosphorylation / response to nicotine / circadian rhythm / brain development / response to hydrogen peroxide / multicellular organism growth / mitochondrial membrane / response to organic cyclic compound / aerobic respiration / mitochondrial intermembrane space / negative regulation of cell growth / cognition / 2 iron, 2 sulfur cluster binding / positive regulation of protein catabolic process / NAD binding / FMN binding / myelin sheath / nervous system development / 4 iron, 4 sulfur cluster binding 類似検索 - 分子機能 | ||||||||||||
生物種 | Mus musculus (ハツカネズミ) / Mouse (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: 3.1 Å | ||||||||||||
データ登録者 | Bridges HR / Blaza JN / Agip ANA / Hirst J | ||||||||||||
資金援助 | 英国, 3件
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引用 | ジャーナル: Nat Commun / 年: 2020 タイトル: Structure of inhibitor-bound mammalian complex I. 著者: Hannah R Bridges / Justin G Fedor / James N Blaza / Andrea Di Luca / Alexander Jussupow / Owen D Jarman / John J Wright / Ahmed-Noor A Agip / Ana P Gamiz-Hernandez / Maxie M Roessler / Ville ...著者: Hannah R Bridges / Justin G Fedor / James N Blaza / Andrea Di Luca / Alexander Jussupow / Owen D Jarman / John J Wright / Ahmed-Noor A Agip / Ana P Gamiz-Hernandez / Maxie M Roessler / Ville R I Kaila / Judy Hirst / 要旨: Respiratory complex I (NADH:ubiquinone oxidoreductase) captures the free energy from oxidising NADH and reducing ubiquinone to drive protons across the mitochondrial inner membrane and power ...Respiratory complex I (NADH:ubiquinone oxidoreductase) captures the free energy from oxidising NADH and reducing ubiquinone to drive protons across the mitochondrial inner membrane and power oxidative phosphorylation. Recent cryo-EM analyses have produced near-complete models of the mammalian complex, but leave the molecular principles of its long-range energy coupling mechanism open to debate. Here, we describe the 3.0-Å resolution cryo-EM structure of complex I from mouse heart mitochondria with a substrate-like inhibitor, piericidin A, bound in the ubiquinone-binding active site. We combine our structural analyses with both functional and computational studies to demonstrate competitive inhibitor binding poses and provide evidence that two inhibitor molecules bind end-to-end in the long substrate binding channel. Our findings reveal information about the mechanisms of inhibition and substrate reduction that are central for understanding the principles of energy transduction in mammalian complex I. | ||||||||||||
履歴 |
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-構造の表示
ムービー |
ムービービューア |
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構造ビューア | EMマップ: SurfViewMolmilJmol/JSmol |
添付画像 |
-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_11377.map.gz | 326.1 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-11377-v30.xml emd-11377.xml | 65.6 KB 65.6 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_11377_fsc.xml | 15.9 KB | 表示 | FSCデータファイル |
画像 | emd_11377.png | 53.4 KB | ||
マスクデータ | emd_11377_msk_1.map | 347.6 MB | マスクマップ | |
その他 | emd_11377_half_map_1.map.gz emd_11377_half_map_2.map.gz | 278.1 MB 277.9 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-11377 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-11377 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_11377_validation.pdf.gz | 487.4 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_11377_full_validation.pdf.gz | 486.5 KB | 表示 | |
XML形式データ | emd_11377_validation.xml.gz | 21.2 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-11377 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-11377 | HTTPS FTP |
-関連構造データ
-リンク
EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
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「今月の分子」の関連する項目 |
-マップ
ファイル | ダウンロード / ファイル: emd_11377.map.gz / 形式: CCP4 / 大きさ: 347.6 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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ボクセルのサイズ | X=Y=Z: 1.054 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
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-添付データ
-マスク #1
ファイル | emd_11377_msk_1.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: #1
ファイル | emd_11377_half_map_1.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: #2
ファイル | emd_11377_half_map_2.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-試料の構成要素
+全体 : Respiratory complex I
+超分子 #1: Respiratory complex I
+分子 #1: NADH-ubiquinone oxidoreductase chain 3
+分子 #2: NADH dehydrogenase [ubiquinone] iron-sulfur protein 7, mitochondrial
+分子 #3: NADH dehydrogenase [ubiquinone] iron-sulfur protein 3, mitochondrial
+分子 #4: NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial
+分子 #5: NADH dehydrogenase [ubiquinone] flavoprotein 2, mitochondrial
+分子 #6: NADH dehydrogenase [ubiquinone] flavoprotein 1, mitochondrial
+分子 #7: NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial
+分子 #8: NADH-ubiquinone oxidoreductase chain 1
+分子 #9: NADH dehydrogenase [ubiquinone] iron-sulfur protein 8, mitochondrial
+分子 #10: NADH-ubiquinone oxidoreductase chain 6
+分子 #11: NADH-ubiquinone oxidoreductase chain 4L
+分子 #12: NADH-ubiquinone oxidoreductase chain 5
+分子 #13: NADH-ubiquinone oxidoreductase chain 4
+分子 #14: NADH-ubiquinone oxidoreductase chain 2
+分子 #15: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 10, mi...
+分子 #16: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 9, mit...
+分子 #17: NADH dehydrogenase [ubiquinone] iron-sulfur protein 4, mitochondrial
+分子 #18: NADH dehydrogenase [ubiquinone] iron-sulfur protein 6, mitochondrial
+分子 #19: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 2
+分子 #20: Acyl carrier protein, mitochondrial
+分子 #21: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 5
+分子 #22: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 6
+分子 #23: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 8
+分子 #24: MCG5603
+分子 #25: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 13
+分子 #26: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 1
+分子 #27: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 3
+分子 #28: NADH dehydrogenase [ubiquinone] 1 subunit C1, mitochondrial
+分子 #29: NADH dehydrogenase [ubiquinone] 1 subunit C2
+分子 #30: NADH dehydrogenase [ubiquinone] iron-sulfur protein 5
+分子 #31: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 1
+分子 #32: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 11, mit...
+分子 #33: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 5, mito...
+分子 #34: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 6
+分子 #35: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 2, mito...
+分子 #36: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 3
+分子 #37: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 8, mito...
+分子 #38: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 4
+分子 #39: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 9
+分子 #40: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 7
+分子 #41: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 10
+分子 #42: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 12
+分子 #43: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 7
+分子 #44: NADH dehydrogenase [ubiquinone] flavoprotein 3, mitochondrial
+分子 #45: IRON/SULFUR CLUSTER
+分子 #46: 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE
+分子 #47: FE2/S2 (INORGANIC) CLUSTER
+分子 #48: FLAVIN MONONUCLEOTIDE
+分子 #49: 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOETHANOLAMINE
+分子 #50: CARDIOLIPIN
+分子 #51: ADENOSINE-5'-TRIPHOSPHATE
+分子 #52: NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE
+分子 #53: ZINC ION
+分子 #54: ~{S}-[2-[3-[[(2~{R})-3,3-dimethyl-2-oxidanyl-4-phosphonooxy-butan...
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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解析 | 単粒子再構成法 |
試料の集合状態 | particle |
-試料調製
濃度 | 3 mg/mL | ||||||||||||
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緩衝液 | pH: 7.14 構成要素:
詳細: pH corrected at room temperature | ||||||||||||
グリッド | モデル: UltrAuFoil R0.6/1 / 材質: GOLD / メッシュ: 300 / 支持フィルム - 材質: GOLD / 支持フィルム - トポロジー: HOLEY / 前処理 - タイプ: GLOW DISCHARGE / 前処理 - 雰囲気: AIR 詳細: The grid was treated for 48 hours in an anaerobic glovebox in ethanol containing 5 mM 11-mercaptoundecylhexaethyleneglycol, washed in ethanol three times and air dried prior to use. | ||||||||||||
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 100 % / 装置: FEI VITROBOT MARK IV / 詳細: blot for 10 seconds before plunging. |
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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撮影 | フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) 検出モード: COUNTING / デジタル化 - サイズ - 横: 3838 pixel / デジタル化 - サイズ - 縦: 3710 pixel / デジタル化 - 画像ごとのフレーム数: 1-12 / 撮影したグリッド数: 1 / 平均電子線量: 50.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD / Cs: 2.7 mm / 最大 デフォーカス(公称値): 3.1 µm / 最小 デフォーカス(公称値): 1.5 µm / 倍率(公称値): 47600 |
試料ステージ | 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER ホルダー冷却材: NITROGEN |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |