+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 ...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 / lipid droplet disassembly / Lipophagy / regulation of bile acid secretion / positive regulation of skeletal muscle tissue development / CAMKK-AMPK signaling cascade / import into nucleus / cAMP-dependent protein kinase regulator activity / regulation of vesicle-mediated transport / positive regulation of cholesterol biosynthetic process / nucleotide-activated protein kinase complex / cellular response to organonitrogen compound / Energy dependent regulation of mTOR by LKB1-AMPK / Carnitine metabolism / negative regulation of hepatocyte apoptotic process / tau-protein kinase / protein kinase regulator activity / bile acid and bile salt transport / cellular response to ethanol / protein localization to lipid droplet / negative regulation of TOR signaling / bile acid signaling pathway / Activation of PPARGC1A (PGC-1alpha) by phosphorylation / motor behavior / response to caffeine / regulation of glycolytic process / positive regulation of protein targeting to mitochondrion / lipid biosynthetic process / cAMP-dependent protein kinase activity / AMP-activated protein kinase activity / negative regulation of tubulin deacetylation / Macroautophagy / positive regulation of protein localization / tau-protein kinase activity / AMP binding / cholesterol biosynthetic process / fatty acid oxidation / cellular response to nutrient levels / carbohydrate transmembrane transporter activity / maltose binding / maltose transport / maltodextrin transmembrane transport / positive regulation of protein kinase activity / fatty acid homeostasis / negative regulation of lipid catabolic process / cellular response to glucose starvation / positive regulation of autophagy / energy homeostasis / regulation of microtubule cytoskeleton organization / Activation of AMPK downstream of NMDARs / ATP-binding cassette (ABC) transporter complex, substrate-binding subunit-containing / response to UV / negative regulation of TORC1 signaling / positive regulation of adipose tissue development / cellular response to calcium ion / negative regulation of insulin receptor signaling pathway / positive regulation of glycolytic process / response to activity / Translocation of SLC2A4 (GLUT4) to the plasma membrane / cellular response to glucose stimulus / response to gamma radiation / TP53 Regulates Metabolic Genes / tau protein binding / regulation of circadian rhythm / ADP binding / Wnt signaling pathway / autophagy / fatty acid biosynthetic process / cellular response to hydrogen peroxide / neuron cellular homeostasis / response to estrogen / cellular response to prostaglandin E stimulus / glucose metabolic process / rhythmic process / cellular response to xenobiotic stimulus / glucose homeostasis / positive regulation of cold-induced thermogenesis / cellular response to oxidative stress / cellular response to hypoxia / outer membrane-bounded periplasmic space / spermatogenesis / Regulation of TP53 Activity through Phosphorylation / non-specific serine/threonine protein kinase / response to hypoxia / protein kinase activity / nuclear speck / apical plasma membrane / axon / negative regulation of gene expression / protein phosphorylation 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 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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 |