+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-16516 | ||||||||||||
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タイトル | Cryo-EM structure NDUFS4 knockout complex I from Mus musculus heart (Class 2). | ||||||||||||
マップデータ | globally sharpened consensus map | ||||||||||||
試料 |
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キーワード | NADH ubiquinone oxidoreductase / Complex I / OXIDOREDUCTASE | ||||||||||||
機能・相同性 | 機能・相同性情報 Mitochondrial Fatty Acid Beta-Oxidation / Complex I biogenesis / reproductive system development / Mitochondrial protein import / Respiratory electron transport / Glyoxylate metabolism and glycine degradation / RHOG GTPase cycle / protein insertion into mitochondrial inner membrane / circulatory system development / blastocyst hatching ...Mitochondrial Fatty Acid Beta-Oxidation / Complex I biogenesis / reproductive system development / Mitochondrial protein import / Respiratory electron transport / Glyoxylate metabolism and glycine degradation / RHOG GTPase cycle / protein insertion into mitochondrial inner membrane / circulatory system development / blastocyst hatching / 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 / : / [2Fe-2S] cluster assembly / oxygen sensor activity / deoxynucleoside kinase activity / negative regulation of non-canonical NF-kappaB signal transduction / 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 / positive regulation of ATP biosynthetic process / mitochondrial translation / NADH:ubiquinone reductase (H+-translocating) / positive regulation of execution phase of apoptosis / apoptotic mitochondrial changes / mitochondrial ATP synthesis coupled electron transport / : / mitochondrial electron transport, NADH to ubiquinone / proton motive force-driven mitochondrial ATP synthesis / mitochondrial respiratory chain complex I assembly / ubiquinone binding / acyl binding / NADH dehydrogenase (ubiquinone) activity / acyl carrier activity / cellular response to interferon-beta / quinone binding / electron transport coupled proton transport / ATP synthesis coupled electron transport / muscle contraction / negative regulation of reactive oxygen species biosynthetic process / negative regulation of intrinsic apoptotic signaling pathway / ATP metabolic process / cellular response to retinoic acid / extrinsic apoptotic signaling pathway / : / aerobic respiration / Neutrophil degranulation / respiratory electron transport chain / reactive oxygen species metabolic process / neurogenesis / cerebellum development / response to hormone / regulation of mitochondrial membrane potential / mitochondrion organization / fatty acid metabolic process / response to cocaine / kidney development / synaptic membrane / mitochondrial membrane / apoptotic signaling pathway / electron transport chain / ionotropic glutamate receptor binding / response to nicotine / response to hydrogen peroxide / multicellular organism growth / mitochondrial intermembrane space / response to organic cyclic compound / negative regulation of cell growth / 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 / response to ethanol / in utero embryonic development / response to oxidative stress / mitochondrial inner membrane / electron transfer activity / response to hypoxia / nuclear body / nuclear speck / structural constituent of ribosome / mitochondrial matrix / response to xenobiotic stimulus 類似検索 - 分子機能 | ||||||||||||
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: 3.2 Å | ||||||||||||
データ登録者 | Yin Z / Bridges HR / Agip ANA / Hirst J | ||||||||||||
資金援助 | 英国, 3件
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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 |
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-構造の表示
添付画像 |
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-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_16516.map.gz | 322.9 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-16516-v30.xml emd-16516.xml | 59.7 KB 59.7 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_16516_fsc.xml | 15.8 KB | 表示 | FSCデータファイル |
画像 | emd_16516.png | 122.6 KB | ||
マスクデータ | emd_16516_msk_1.map | 347.6 MB | マスクマップ | |
Filedesc metadata | emd-16516.cif.gz | 13.9 KB | ||
その他 | emd_16516_half_map_1.map.gz emd_16516_half_map_2.map.gz | 323 MB 323 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-16516 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-16516 | 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_16516.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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注釈 | globally sharpened consensus map | ||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.352 Å | ||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||
詳細 | EMDB XML:
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-添付データ
-マスク #1
ファイル | emd_16516_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: half map 1
ファイル | emd_16516_half_map_1.map | ||||||||||||
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注釈 | half map 1 | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: half map 2
ファイル | emd_16516_half_map_2.map | ||||||||||||
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注釈 | half map 2 | ||||||||||||
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 : Very long-chain specific acyl-CoA dehydrogenase, mitochondrial
+超分子 #1: Very long-chain specific acyl-CoA dehydrogenase, mitochondrial
+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 6, mitochondrial
+分子 #18: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 2
+分子 #19: Acyl carrier protein, mitochondrial
+分子 #20: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 5
+分子 #21: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 6
+分子 #22: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 8
+分子 #23: MCG5603
+分子 #24: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 13
+分子 #25: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 1
+分子 #26: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 3
+分子 #27: NADH dehydrogenase [ubiquinone] 1 subunit C1, mitochondrial
+分子 #28: NADH dehydrogenase [ubiquinone] 1 subunit C2
+分子 #29: NADH dehydrogenase [ubiquinone] iron-sulfur protein 5
+分子 #30: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 1
+分子 #31: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 11, mit...
+分子 #32: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 5, mito...
+分子 #33: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 6
+分子 #34: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 2, mito...
+分子 #35: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 3
+分子 #36: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 8, mito...
+分子 #37: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 4
+分子 #38: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 9
+分子 #39: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 7
+分子 #40: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 10
+分子 #41: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 7
+分子 #42: NADH dehydrogenase [ubiquinone] flavoprotein 3, mitochondrial
+分子 #43: IRON/SULFUR CLUSTER
+分子 #44: 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE
+分子 #45: FE2/S2 (INORGANIC) CLUSTER
+分子 #46: FLAVIN MONONUCLEOTIDE
+分子 #47: Ubiquinone-9
+分子 #48: 1,2-Distearoyl-sn-glycerophosphoethanolamine
+分子 #49: CARDIOLIPIN
+分子 #50: DODECYL-BETA-D-MALTOSIDE
+分子 #51: GUANOSINE-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 | 3.82 mg/mL | |||||||||||||||
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緩衝液 | pH: 7.14 構成要素:
詳細: pH was corrected at room temperature ~22 C | |||||||||||||||
グリッド | モデル: UltrAuFoil / 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 - 時間: 90 sec. / 前処理 - 雰囲気: AIR 詳細: The grid was also covalently modified by 48 hour incubation in 5 mM HS-C11-EG6 in ethanol in an anoxic glovebox, and washed thrice in ethanol before air drying. | |||||||||||||||
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 100 % / チャンバー内温度: 277 K / 装置: FEI VITROBOT MARK IV |
-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 K3 BIOQUANTUM (6k x 4k) 平均電子線量: 45.0 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 / 最大 デフォーカス(公称値): 2.9 µm / 最小 デフォーカス(公称値): 1.5 µm |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |