+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-22337 | |||||||||
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タイトル | Cryo-EM structure of ATP-bound fully inactive AMPK in complex with Fab and nanobody | |||||||||
マップデータ | Structure of AMPK with Fab and nanobody | |||||||||
試料 |
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機能・相同性 | 機能・相同性情報 negative regulation of glucosylceramide biosynthetic process / positive regulation of mitochondrial transcription / [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase / [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase activity / regulation of stress granule assembly / histone H2BS36 kinase activity / AMPK inhibits chREBP transcriptional activation activity / regulation of peptidyl-serine phosphorylation / cold acclimation / positive regulation of peptidyl-lysine acetylation ...negative regulation of glucosylceramide biosynthetic process / positive regulation of mitochondrial transcription / [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase / [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase activity / regulation of stress granule assembly / histone H2BS36 kinase activity / AMPK inhibits chREBP transcriptional activation activity / regulation of peptidyl-serine phosphorylation / cold acclimation / positive regulation of peptidyl-lysine acetylation / bile acid signaling pathway / lipid droplet disassembly / Lipophagy / regulation of bile acid secretion / positive regulation of skeletal muscle tissue development / import into nucleus / CAMKK-AMPK signaling cascade / cAMP-dependent protein kinase regulator activity / regulation of vesicle-mediated transport / positive regulation of cholesterol biosynthetic process / nucleotide-activated protein kinase complex / positive regulation of T cell mediated immune response to tumor cell / : / Energy dependent regulation of mTOR by LKB1-AMPK / Carnitine shuttle / negative regulation of hepatocyte apoptotic process / tau-protein kinase / protein kinase regulator activity / cellular response to ethanol / negative regulation of TOR signaling / protein localization to lipid droplet / bile acid and bile salt transport / Activation of PPARGC1A (PGC-1alpha) by phosphorylation / response to caffeine / regulation of glycolytic process / motor behavior / positive regulation of protein targeting to mitochondrion / cAMP-dependent protein kinase activity / lipid biosynthetic process / AMP-activated protein kinase activity / tau-protein kinase activity / negative regulation of tubulin deacetylation / Macroautophagy / cholesterol biosynthetic process / AMP binding / fatty acid oxidation / maltose binding / maltose transport / maltodextrin transmembrane transport / carbohydrate transmembrane transporter activity / positive regulation of protein kinase activity / fatty acid homeostasis / negative regulation of lipid catabolic process / cellular response to nutrient levels / cellular response to glucose starvation / regulation of microtubule cytoskeleton organization / ATP-binding cassette (ABC) transporter complex, substrate-binding subunit-containing / positive regulation of autophagy / Activation of AMPK downstream of NMDARs / response to UV / positive regulation of protein localization / energy homeostasis / negative regulation of insulin receptor signaling pathway / negative regulation of TORC1 signaling / positive regulation of adipose tissue development / cellular response to calcium ion / positive regulation of glycolytic process / response to gamma radiation / response to activity / Translocation of SLC2A4 (GLUT4) to the plasma membrane / TP53 Regulates Metabolic Genes / cellular response to glucose stimulus / ADP binding / regulation of circadian rhythm / tau protein binding / Wnt signaling pathway / autophagy / fatty acid biosynthetic process / cellular response to hydrogen peroxide / response to estrogen / neuron cellular homeostasis / glucose metabolic process / cellular response to prostaglandin E stimulus / positive regulation of T cell activation / rhythmic process / positive regulation of cold-induced thermogenesis / cellular response to xenobiotic stimulus / glucose homeostasis / cellular response to oxidative stress / outer membrane-bounded periplasmic space / cellular response to hypoxia / spermatogenesis / Regulation of TP53 Activity through Phosphorylation / response to hypoxia / non-specific serine/threonine protein kinase / protein kinase activity / nuclear speck / protein phosphorylation / apical plasma membrane / axon 類似検索 - 分子機能 | |||||||||
生物種 | Homo sapiens (ヒト) / synthetic construct (人工物) / Escherichia coli K-12 (大腸菌) | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.92 Å | |||||||||
データ登録者 | Yan Y / Murkherjee S / Zhou XE / Xu TH / Xu HE / Kossiakoff AA / Melcher K | |||||||||
資金援助 | 米国, 2件
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引用 | ジャーナル: Science / 年: 2021 タイトル: Structure of an AMPK complex in an inactive, ATP-bound state. 著者: Yan Yan / Somnath Mukherjee / Kaleeckal G Harikumar / Timothy S Strutzenberg / X Edward Zhou / Kelly Suino-Powell / Ting-Hai Xu / Ryan D Sheldon / Jared Lamp / Joseph S Brunzelle / Katarzyna ...著者: Yan Yan / Somnath Mukherjee / Kaleeckal G Harikumar / Timothy S Strutzenberg / X Edward Zhou / Kelly Suino-Powell / Ting-Hai Xu / Ryan D Sheldon / Jared Lamp / Joseph S Brunzelle / Katarzyna Radziwon / Abigail Ellis / Scott J Novick / Irving E Vega / Russell G Jones / Laurence J Miller / H Eric Xu / Patrick R Griffin / Anthony A Kossiakoff / Karsten Melcher / 要旨: Adenosine monophosphate (AMP)-activated protein kinase (AMPK) regulates metabolism in response to the cellular energy states. Under energy stress, AMP stabilizes the active AMPK conformation, in ...Adenosine monophosphate (AMP)-activated protein kinase (AMPK) regulates metabolism in response to the cellular energy states. Under energy stress, AMP stabilizes the active AMPK conformation, in which the kinase activation loop (AL) is protected from protein phosphatases, thus keeping the AL in its active, phosphorylated state. At low AMP:ATP (adenosine triphosphate) ratios, ATP inhibits AMPK by increasing AL dynamics and accessibility. We developed conformation-specific antibodies to trap ATP-bound AMPK in a fully inactive, dynamic state and determined its structure at 3.5-angstrom resolution using cryo-electron microscopy. A 180° rotation and 100-angstrom displacement of the kinase domain fully exposes the AL. On the basis of the structure and supporting biophysical data, we propose a multistep mechanism explaining how adenine nucleotides and pharmacological agonists modulate AMPK activity by altering AL phosphorylation and accessibility. | |||||||||
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_22337.map.gz | 4.7 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-22337-v30.xml emd-22337.xml | 23.2 KB 23.2 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_22337_fsc.xml | 8.6 KB | 表示 | FSCデータファイル |
画像 | emd_22337.png | 162 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-22337 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-22337 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_22337_validation.pdf.gz | 355.9 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_22337_full_validation.pdf.gz | 355.5 KB | 表示 | |
XML形式データ | emd_22337_validation.xml.gz | 10.4 KB | 表示 | |
CIF形式データ | emd_22337_validation.cif.gz | 13.6 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-22337 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-22337 | 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_22337.map.gz / 形式: CCP4 / 大きさ: 52.7 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | Structure of AMPK with Fab and nanobody | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
投影像・断面図 | 画像のコントロール
画像は Spider により作成 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.029 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
-試料の構成要素
+全体 : AMPK complex with Fab and nanobody
+超分子 #1: AMPK complex with Fab and nanobody
+超分子 #2: AMPK
+超分子 #3: Fab, nanobody
+分子 #1: 5'-AMP-activated protein kinase catalytic subunit alpha-1
+分子 #2: 5'-AMP-activated protein kinase subunit beta-2
+分子 #3: 5'-AMP-activated protein kinase subunit gamma-1
+分子 #4: Maltodextrin-binding protein
+分子 #5: Fab light chain
+分子 #6: Fab heavy chain
+分子 #7: Nanobody
+分子 #9: ADENOSINE-5'-TRIPHOSPHATE
+分子 #10: ADENOSINE-5'-DIPHOSPHATE
+分子 #11: ADENOSINE MONOPHOSPHATE
-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
緩衝液 | pH: 8 |
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グリッド | 詳細: unspecified |
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 100 % / チャンバー内温度: 281 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 K2 SUMMIT (4k x 4k) 検出モード: SUPER-RESOLUTION / 実像数: 7659 / 平均露光時間: 0.2 sec. / 平均電子線量: 88.0 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 |
試料ステージ | ホルダー冷却材: NITROGEN |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |