ArticleThe Journal of biological chemistry2017
Deconvoluting AMP-activated protein kinase (AMPK) adenine nucleotide binding and sensing.
Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 53 citations in OpenAlex.
- A conserved archaeal protein with evolutionary links to bacterial ribosome hibernation and eukaryotic energy sensing.The EMBO journal · 2026Article
- AMPK-Directed Therapeutics for MASLD: Mechanistic Rationale, Activator Classes, and Clinical Translation.International journal of molecular sciences · 2026Review
- Binding of 14-3-3 stabilises recombinant AMPKγ2-containing complexes.The Biochemical journal · 2026Article
- Structural Heterogeneity of Proteoform-Ligand Complexes in Adenosine Monophosphate-Activated Protein Kinase Uncovered by Integrated Top-Down Mass Spectrometry.Journal of the American Chemical Society · 2025Article
- Role of AMP-Activated Protein Kinase (AMPK) in Female Reproduction: A Review.International journal of molecular sciences · 2025Review
- Small Molecule Modulators of AMP-Activated Protein Kinase (AMPK) Activity and Their Potential in Cancer Therapy.Journal of medicinal chemistry · 2025Review
- Assays of Different Mechanisms of AMPK Activation, and Use of Cells Expressing Mutant AMPK to Delineate Activation Mechanisms.Methods in molecular biology (Clifton, N.J.) · 2025Article
- The metabolic sensor AMPK: Twelve enzymes in one.Molecular metabolism · 2024Review
- Does AMPK bind glycogen in skeletal muscle or is the relationship correlative?Essays in biochemistry · 2024Review
- Role of AMPK and Sirtuins in Aging Heart: Basic and Translational Aspects.Aging and disease · 2024Review
- Article
- Syntheses and Applications of Coumarin-Derived Fluorescent Probes for Real-Time Monitoring of NAD(P)H Dynamics in Living Cells across Diverse Chemical Environments.ACS applied bio materials · 2024Article
- AMP-activated protein kinase can be allosterically activated by ADP but AMP remains the key activating ligand.The Biochemical journal · 2024Article
- BAY-3827 and SBI-0206965: Potent AMPK Inhibitors That Paradoxically Increase Thr172 Phosphorylation.International journal of molecular sciences · 2023Article
- Frequent loss-of-function mutations in the AMPK-α2 catalytic subunit suggest a tumour suppressor role in human skin cancers.The Biochemical journal · 2023Article
- Multi-Omics Analysis Reveals Mechanisms of Strong Phosphorus Adaptation in Tea Plant Roots.International journal of molecular sciences · 2023Article
- New insights into activation and function of the AMPK.Nature reviews. Molecular cell biology · 2023Review
- Rapid metabolic reprogramming mediated by the AMP-activated protein kinase during the lytic cycle of Toxoplasma gondii.Nature communications · 2023Article
- Protein-Metabolite Interactions Shape Cellular Metabolism and Physiology.Methods in molecular biology (Clifton, N.J.) · 2023Article
- The aldolase inhibitor aldometanib mimics glucose starvation to activate lysosomal AMPK.Nature metabolism · 2022Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 3 countries.
Funding
Abstract
AMP-activated protein kinase (AMPK) is a central cellular energy sensor that adapts metabolism and growth to the energy state of the cell. AMPK senses the ratio of adenine nucleotides (adenylate energy charge) by competitive binding of AMP, ADP, and ATP to three sites (CBS1, CBS3, and CBS4) in its γ-subunit. Because these three binding sites are functionally interconnected, it remains unclear how nucleotides bind to individual sites, which nucleotides occupy each site under physiological conditions, and how binding to one site affects binding to the other sites. Here, we comprehensively analyze nucleotide binding to wild-type and mutant AMPK protein complexes by quantitative competition assays and by hydrogen-deuterium exchange MS. We also demonstrate that NADPH, in addition to the known AMPK ligand NADH, directly and competitively binds AMPK at the AMP-sensing CBS3 site. Our findings reveal how AMP binding to one site affects the conformation and adenine nucleotide binding at the other two sites and establish CBS3, and not CBS1, as the high affinity exchangeable AMP/ADP/ATP-binding site. We further show that AMP binding at CBS4 increases AMP binding at CBS3 by 2 orders of magnitude and reverses the AMP/ATP preference of CBS3. Together, these results illustrate how the three CBS sites collaborate to enable highly sensitive detection of cellular energy states to maintain the tight ATP homeostastis required for cellular metabolism.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.