Structure of an AMPK complex in an inactive, ATP-bound state

doi:10.1126/science.abe7565

GSTDTAP > 气候变化

DOI	10.1126/science.abe7565
	Structure of an AMPK complex in an inactive, ATP-bound state
	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
	2021-07-23
发表期刊	Science
出版年	2021
英文摘要	AMP-activated protein kinase (AMPK) is a key sensor of energy status in eukaryotes. Its dynamic structure is regulated by allosteric factors including phosphorylation and binding of nucleotides and metabolites. Yan et al. developed conformation-specific antibodies that trap AMPK in a fully inactive state that has experienced a large, domain-level rotation. Biophysical experiments in cells and in vitro are consistent with the structural work and support a model in which the activation loop is fully exposed in the completely inactive, dephosphorylated state. These structures inform our understanding of the complex allosteric behavior in this crucial metabolic regulator. Science , abe7565, this issue p. [413][1] 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. [1]: /lookup/doi/10.1126/science.abe7565
领域	气候变化 ; 资源环境
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文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/334479
专题	气候变化资源环境科学
推荐引用方式 GB/T 7714	Yan Yan,Somnath Mukherjee,Kaleeckal G. Harikumar,et al. Structure of an AMPK complex in an inactive, ATP-bound state[J]. Science,2021.
APA	Yan Yan.,Somnath Mukherjee.,Kaleeckal G. Harikumar.,Timothy S. Strutzenberg.,X. Edward Zhou.,...&Karsten Melcher.(2021).Structure of an AMPK complex in an inactive, ATP-bound state.Science.
MLA	Yan Yan,et al."Structure of an AMPK complex in an inactive, ATP-bound state".Science (2021).