Evidence map›Paper›PMID 34437114›Full record

ArticleScience (New York, N.Y.)2021

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 and 10 more

Open access · greenAbstract read
In one paragraph

Article in Science (New York, N.Y.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.

0numbers the graph read from it
0cells of the map it votes in
69citing papers in PubMed
6.9field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

69 citing papers in PubMed, 115 citations in OpenAlex.

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  9. Conformational ensembles of the magnesium channel CorA reveal structural basis for channel gating.Proceedings of the National Academy of Sciences of the United States of America · 2026
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9 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

20 authors at 7 institutions in 3 countries.

Yan YanDepartment of Structural Biology, Van Andel Institute, Grand Rapids, MI 49503, USA.ORCID 0000-0001-6656-7737
Somnath Mukherjee *Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637, USA.ORCID 0000-0001-5447-4496
Kaleeckal G Harikumar *Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Scottsdale, AZ 85259, USA.ORCID 0000-0003-0411-5334
Timothy S Strutzenberg *Department of Molecular Medicine, The Scripps Research Institute, Scripps Florida, Jupiter, FL 33458, USA.ORCID 0000-0003-0598-534X
X Edward Zhou *Department of Structural Biology, Van Andel Institute, Grand Rapids, MI 49503, USA.ORCID 0000-0003-3829-6137
Kelly Suino-PowellDepartment of Structural Biology, Van Andel Institute, Grand Rapids, MI 49503, USA.
Ting-Hai XuDepartment of Structural Biology, Van Andel Institute, Grand Rapids, MI 49503, USA.ORCID 0000-0003-2239-1420
Ryan D SheldonMetabolic and Nutritional Programming, Center for Cancer and Cell Biology, Van Andel Institute, Grand Rapids, MI 49503, USA.ORCID 0000-0002-1573-9719
Jared LampIntegrated Mass Spectrometry Unit, Department of Translational Neuroscience, Michigan State University College of Human Medicine, Grand Rapids Research Center, Grand Rapids, MI 49503, USA.ORCID 0000-0002-7187-7657
Joseph S BrunzelleLife Sciences Collaborative Access Team, Northwestern University Synchrotron Research Center, Northwestern University, Argonne, IL 60439, USA.ORCID 0000-0001-9197-0018
Katarzyna RadziwonDepartment of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637, USA.
Abigail EllisMetabolic and Nutritional Programming, Center for Cancer and Cell Biology, Van Andel Institute, Grand Rapids, MI 49503, USA.ORCID 0000-0002-8736-8283
Scott J NovickDepartment of Molecular Medicine, The Scripps Research Institute, Scripps Florida, Jupiter, FL 33458, USA.ORCID 0000-0003-0213-3897
Irving E VegaIntegrated Mass Spectrometry Unit, Department of Translational Neuroscience, Michigan State University College of Human Medicine, Grand Rapids Research Center, Grand Rapids, MI 49503, USA.
Russell G JonesMetabolic and Nutritional Programming, Center for Cancer and Cell Biology, Van Andel Institute, Grand Rapids, MI 49503, USA.ORCID 0000-0003-2250-4675
Laurence J MillerDepartment of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Scottsdale, AZ 85259, USA.ORCID 0000-0002-4554-3872
H Eric XuCenter for Structure and Function of Drug Targets, The CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences (CAS), Shanghai 201203, China.ORCID 0000-0002-6829-8144
Patrick R GriffinDepartment of Molecular Medicine, The Scripps Research Institute, Scripps Florida, Jupiter, FL 33458, USA.ORCID 0000-0002-3404-690X
Anthony A KossiakoffDepartment of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637, USA.
Karsten MelcherDepartment of Structural Biology, Van Andel Institute, Grand Rapids, MI 49503, USA. karsten.melcher@vai.org.ORCID 0000-0002-9125-4027
Van Andel Institute · USScripps Research Institute · USUniversity of Chicago · USGrand Rapids Community College · USMayo Clinic in Arizona · USNorthwestern University · PHShanghai Institute of Materia Medica · CN

Funding

Chaperone-Assisted Structure Determination of Membrane ProteinsR01GM117372 · NIGMS · UNIVERSITY OF CHICAGO · PI ANTHONY A KOSSIAKOFF · 2016 to 2026
$4.0M
Structural Mechanisms of AMPK RegulationR01GM129436 · NIGMS · VAN ANDEL RESEARCH INSTITUTE · PI MELCHER, KARSTEN · 2018 to 2019
$767k
NIGMS NIH HHS R01 GM117372NIGMS NIH HHS R01 GM129436
6 · The paper itself

Abstract

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.

Indexed as

Adenosine MonophosphateAdenosine TriphosphateAMP-Activated Protein KinasesCryoelectron MicroscopyHumansImmunoglobulin Fab FragmentsModels, MolecularPhosphorylationProtein ConformationProtein DomainsProtein Engineeringadenosine 5'-O-(3-thiotriphosphate)Adenosine MonophosphateAdenosine TriphosphateAMP-Activated Protein KinasesImmunoglobulin Fab Fragments

Identifiers

PMID34437114
PMCPMC8428800
OpenAlexW3183158529

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.