登録情報 データベース : EMDB / ID : EMD-22337 構造の表示 ダウンロードとリンクタイトル 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 詳細 試料複合体 : AMPK complex with Fab and nanobody複合体 : AMPKタンパク質・ペプチド : 5'-AMP-activated protein kinase catalytic subunit alpha-1タンパク質・ペプチド : 5'-AMP-activated protein kinase subunit beta-2タンパク質・ペプチド : 5'-AMP-activated protein kinase subunit gamma-1タンパク質・ペプチド : Maltodextrin-binding protein複合体 : Fab, nanobodyタンパク質・ペプチド : Fab light chainタンパク質・ペプチド : Fab heavy chainタンパク質・ペプチド : Nanobodyリガンド : ADENOSINE-5'-TRIPHOSPHATEリガンド : ADENOSINE-5'-DIPHOSPHATEリガンド : ADENOSINE MONOPHOSPHATE 詳細 キーワード AMPK / ATP / fully inactive / KD-displaced / TRANSFERASE-IMMUNE SYSTEM complex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
negative regulation of glucosylceramide biosynthetic process / [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase / [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase activity / regulation of stress granule assembly / positive regulation of mitochondrial transcription / AMPK inhibits chREBP transcriptional activation activity / histone H2BS36 kinase activity / cold acclimation / cAMP-dependent protein kinase regulator activity / AMP-activated protein kinase activity ... negative regulation of glucosylceramide biosynthetic process / [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase / [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase activity / regulation of stress granule assembly / positive regulation of mitochondrial transcription / AMPK inhibits chREBP transcriptional activation activity / histone H2BS36 kinase activity / cold acclimation / cAMP-dependent protein kinase regulator activity / AMP-activated protein kinase activity / lipid droplet disassembly / Lipophagy / regulation of carbon utilization / positive regulation of skeletal muscle tissue development / CAMKK-AMPK signaling cascade / import into nucleus / regulation of vesicle-mediated transport / nucleotide-activated protein kinase complex / negative regulation of hepatocyte apoptotic process / positive regulation of T cell mediated immune response to tumor cell / Carnitine shuttle / Energy dependent regulation of mTOR by LKB1-AMPK / tau-protein kinase / protein kinase regulator activity / negative regulation of TOR signaling / Activation of PPARGC1A (PGC-1alpha) by phosphorylation / response to caffeine / positive regulation of protein targeting to mitochondrion / cAMP-dependent protein kinase activity / regulation of glycolytic process / protein localization to lipid droplet / tau-protein kinase activity / negative regulation of tubulin deacetylation / AMP binding / cholesterol biosynthetic process / Macroautophagy / lipid biosynthetic process / cellular response to stress / fatty acid oxidation / motor behavior / positive regulation of protein kinase activity / cellular response to ethanol / carbohydrate transmembrane transporter activity / maltose binding / maltose transport / maltodextrin transmembrane transport / fatty acid homeostasis / negative regulation of lipid catabolic process / cellular response to nutrient levels / response to UV / cellular response to glucose starvation / energy homeostasis / Activation of AMPK downstream of NMDARs / ATP-binding cassette (ABC) transporter complex, substrate-binding subunit-containing / positive regulation of protein localization / negative regulation of TORC1 signaling / positive regulation of adipose tissue development / positive regulation of gluconeogenesis / positive regulation of autophagy / negative regulation of insulin receptor signaling pathway / cellular response to calcium ion / regulation of microtubule cytoskeleton organization / positive regulation of glycolytic process / response to activity / response to gamma radiation / TP53 Regulates Metabolic Genes / Translocation of SLC2A4 (GLUT4) to the plasma membrane / cellular response to glucose stimulus / positive regulation of cholesterol biosynthetic process / regulation of circadian rhythm / neuron cellular homeostasis / ADP binding / positive regulation of T cell activation / autophagy / response to estrogen / tau protein binding / Wnt signaling pathway / cellular response to xenobiotic stimulus / cellular response to hydrogen peroxide / glucose metabolic process / fatty acid biosynthetic process / rhythmic process / cellular response to prostaglandin E stimulus / glucose homeostasis / positive regulation of cold-induced thermogenesis / outer membrane-bounded periplasmic space / cellular response to oxidative stress / spermatogenesis / cellular response to hypoxia / Regulation of TP53 Activity through Phosphorylation / response to hypoxia / protein phosphorylation / non-specific serine/threonine protein kinase / protein kinase activity / regulation of cell cycle / nuclear speck / cilium / ciliary basal body / apical plasma membrane / axon 類似検索 - 分子機能 PRKAA1, UBA-like autoinhibitory domain / 5'-AMP-activated protein kinase alpha 1 catalytic subunit, C-terminal / : / AMP-activated protein kinase, alpha subunit, autoinhibitory domain / : / Association with the SNF1 complex (ASC) domain / ASC domain superfamily / : / 5'-AMP-activated protein kinase beta subunit, interaction domain / 5'-AMP-activated protein kinase beta subunit, interation domain ... PRKAA1, UBA-like autoinhibitory domain / 5'-AMP-activated protein kinase alpha 1 catalytic subunit, C-terminal / : / AMP-activated protein kinase, alpha subunit, autoinhibitory domain / : / Association with the SNF1 complex (ASC) domain / ASC domain superfamily / : / 5'-AMP-activated protein kinase beta subunit, interaction domain / 5'-AMP-activated protein kinase beta subunit, interation domain / AMPK, C-terminal adenylate sensor domain / Adenylate sensor of SNF1-like protein kinase / AMP-activated protein kinase, glycogen-binding domain / Glycogen recognition site of AMP-activated protein kinase / KA1 domain/Ssp2, C-terminal / Domain in cystathionine beta-synthase and other proteins. / CBS domain superfamily / CBS domain / CBS domain / CBS domain profile. / Maltose/Cyclodextrin ABC transporter, substrate-binding protein / Solute-binding family 1, conserved site / Bacterial extracellular solute-binding proteins, family 1 signature. / Bacterial extracellular solute-binding protein / Bacterial extracellular solute-binding protein / Immunoglobulin E-set / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. / Protein kinase domain / Serine/Threonine protein kinases, catalytic domain / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Immunoglobulin-like fold / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily 類似検索 - ドメイン・相同性 Maltodextrin-binding protein / 5'-AMP-activated protein kinase subunit beta-2 / 5'-AMP-activated protein kinase subunit gamma-1 / 5'-AMP-activated protein kinase catalytic subunit alpha-1 類似検索 - 構成要素生物種 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 詳細 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 詳細 詳細を隠すOrganization Grant number 国 National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS) R01 GM117372 米国 National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS) R01 GM129436 米国
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 登録 2020年7月20日 - ヘッダ(付随情報) 公開 2021年7月21日 - マップ公開 2021年7月21日 - 更新 2024年11月6日 - 現状 2024年11月6日 処理サイト : RCSB / 状態 : 公開
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