Structure of an AMPK complex in an inactive, ATP-bound state-Reference-Cited by-同舟云学术

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

Published:2021-07-23 Issue:6553 Volume:373 Page:413-419
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Yan Yan¹^ORCID,Mukherjee Somnath²^ORCID,Harikumar Kaleeckal G.³^ORCID,Strutzenberg Timothy S.⁴^ORCID,Zhou X. Edward¹^ORCID,Suino-Powell Kelly¹,Xu Ting-Hai¹⁵^ORCID,Sheldon Ryan D.⁶^ORCID,Lamp Jared⁷^ORCID,Brunzelle Joseph S.⁸^ORCID,Radziwon Katarzyna²,Ellis Abigail⁶^ORCID,Novick Scott J.⁴^ORCID,Vega Irving E.⁷,Jones Russell G.⁶^ORCID,Miller Laurence J.³^ORCID,Xu H. Eric⁹^ORCID,Griffin Patrick R.⁴^ORCID,Kossiakoff Anthony A.²¹⁰,Melcher Karsten¹^ORCID

Affiliation:

1. Department of Structural Biology, Van Andel Institute, Grand Rapids, MI 49503, USA.

2. Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637, USA.

3. Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Scottsdale, AZ 85259, USA.

4. Department of Molecular Medicine, The Scripps Research Institute, Scripps Florida, Jupiter, FL 33458, USA.

5. Center for Epigenetics, Van Andel Institute, Grand Rapids, MI 49503, USA.

6. Metabolic and Nutritional Programming, Center for Cancer and Cell Biology, Van Andel Institute, Grand Rapids, MI 49503, USA.

7. Integrated Mass Spectrometry Unit, Department of Translational Neuroscience, Michigan State University College of Human Medicine, Grand Rapids Research Center, Grand Rapids, MI 49503, USA.

8. Life Sciences Collaborative Access Team, Northwestern University Synchrotron Research Center, Northwestern University, Argonne, IL 60439, USA.

9. Center 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.

10. Institute of Biophysical Dynamics, University of Chicago, Chicago, IL 60637, USA.

Abstract

How to catch a dynamic state 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

Funder

National Institute of General Medical Sciences

Van Andel Research Institute

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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