- EMDB-23708: ATP-bound AMP-activated protein kinase -
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基本情報
登録情報
データベース: EMDB / ID: EMD-23708
タイトル
ATP-bound AMP-activated protein kinase
マップデータ
試料
複合体: MBP-fused ATP bound AMPK in complex with C-compound stabilized by Fab and a nanobody
タンパク質・ペプチド: x 7種
リガンド: x 4種
キーワード
AMPK / activation / ATP-binding / SIGNALING PROTEIN
機能・相同性
機能・相同性情報
AMPK inhibits chREBP transcriptional activation activity / cAMP-dependent protein kinase regulator activity / Lipophagy / regulation of carbon utilization / import into nucleus / nucleotide-activated protein kinase complex / Energy dependent regulation of mTOR by LKB1-AMPK / Carnitine shuttle / protein kinase regulator activity / Activation of PPARGC1A (PGC-1alpha) by phosphorylation ...AMPK inhibits chREBP transcriptional activation activity / cAMP-dependent protein kinase regulator activity / Lipophagy / regulation of carbon utilization / import into nucleus / nucleotide-activated protein kinase complex / Energy dependent regulation of mTOR by LKB1-AMPK / Carnitine shuttle / protein kinase regulator activity / Activation of PPARGC1A (PGC-1alpha) by phosphorylation / regulation of glycolytic process / cAMP-dependent protein kinase activity / Macroautophagy / AMP binding / carbohydrate transmembrane transporter activity / positive regulation of protein kinase activity / cellular response to nutrient levels / cellular response to glucose starvation / Activation of AMPK downstream of NMDARs / positive regulation of gluconeogenesis / Translocation of SLC2A4 (GLUT4) to the plasma membrane / TP53 Regulates Metabolic Genes / ADP binding / fatty acid biosynthetic process / positive regulation of cold-induced thermogenesis / spermatogenesis / Regulation of TP53 Activity through Phosphorylation / periplasmic space / regulation of cell cycle / protein phosphorylation / protein kinase binding / signal transduction / nucleoplasm / ATP binding / nucleus / membrane / cytosol / cytoplasm 類似検索 - 分子機能
: / 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 / AMP-activated protein kinase, glycogen-binding domain / Glycogen recognition site of AMP-activated protein kinase / Domain in cystathionine beta-synthase and other proteins. / CBS domain superfamily ...: / 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 / AMP-activated protein kinase, glycogen-binding domain / Glycogen recognition site of AMP-activated protein kinase / 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 / Immunoglobulin-like fold 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 類似検索 - 構成要素
生物種
Homo sapiens (ヒト) / Escherichia coli (大腸菌) / Lama glama (ラマ)
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.