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 / positive regulation of peptidyl-lysine acetylation / positive regulation of mitochondrial transcription / [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase / [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase activity / regulation of stress granule assembly / AMPK inhibits chREBP transcriptional activation activity / cold acclimation / cAMP-dependent protein kinase regulator activity / lipid droplet disassembly ... negative regulation of glucosylceramide biosynthetic process / positive regulation of peptidyl-lysine acetylation / positive regulation of mitochondrial transcription / [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase / [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase activity / regulation of stress granule assembly / AMPK inhibits chREBP transcriptional activation activity / cold acclimation / cAMP-dependent protein kinase regulator 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 / Energy dependent regulation of mTOR by LKB1-AMPK / positive regulation of T cell mediated immune response to tumor cell / Carnitine shuttle / tau-protein kinase / negative regulation of hepatocyte apoptotic process / cellular response to ethanol / 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 / regulation of glycolytic process / cAMP-dependent protein kinase activity / protein localization to lipid droplet / motor behavior / tau-protein kinase activity / lipid biosynthetic process / negative regulation of tubulin deacetylation / Macroautophagy / cellular response to stress / cholesterol biosynthetic process / AMP binding / fatty acid oxidation / carbohydrate transmembrane transporter activity / maltose binding / positive regulation of protein kinase activity / maltose transport / maltodextrin transmembrane transport / fatty acid homeostasis / cellular response to nutrient levels / negative regulation of lipid catabolic process / response to UV / cellular response to glucose starvation / Activation of AMPK downstream of NMDARs / ATP-binding cassette (ABC) transporter complex, substrate-binding subunit-containing / energy homeostasis / positive regulation of protein localization / positive regulation of adipose tissue development / negative regulation of TORC1 signaling / positive regulation of autophagy / positive regulation of gluconeogenesis / negative regulation of insulin receptor signaling pathway / regulation of microtubule cytoskeleton organization / cellular response to calcium ion / positive regulation of glycolytic process / response to activity / response to gamma radiation / Translocation of SLC2A4 (GLUT4) to the plasma membrane / TP53 Regulates Metabolic Genes / positive regulation of cholesterol biosynthetic process / cellular response to glucose stimulus / regulation of circadian rhythm / ADP binding / tau protein binding / autophagy / positive regulation of T cell activation / cellular response to hydrogen peroxide / Wnt signaling pathway / neuron cellular homeostasis / response to estrogen / glucose metabolic process / fatty acid biosynthetic process / rhythmic process / cellular response to prostaglandin E stimulus / glucose homeostasis / cellular response to xenobiotic stimulus / 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 / eukaryotic translation initiation factor 2alpha kinase activity / 3-phosphoinositide-dependent protein kinase activity / DNA-dependent protein kinase activity / ribosomal protein S6 kinase activity / histone H3S10 kinase activity / histone H2AXS139 kinase activity / histone H3S28 kinase activity / histone H4S1 kinase activity / histone H2BS14 kinase activity / histone H3T3 kinase activity / histone H2AS121 kinase activity 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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