Structural basis of AMPK regulation by adenine nucleotides and glycogen

Li, Xiaodan; Wang, Lili; Zhou, X. Edward; Ke, Jiyuan; de Waal, Parker W.; Gu, Xin; Tan, M. H. Eileen; Wang, Dongye; Wu, Donghai; Xu, H. Eric; Melcher, Karsten

doi:10.1038/cr.2014.150

Title: Structural basis of AMPK regulation by adenine nucleotides and glycogen

Journal Article · Fri Nov 21 00:00:00 EST 2014 · Cell Research

DOI:https://doi.org/10.1038/cr.2014.150· OSTI ID:1169343

Li, Xiaodan ^[1]; Wang, Lili ^[1]; Zhou, X. Edward ^[2]; Ke, Jiyuan ^[2]; de Waal, Parker W. ^[2]; Gu, Xin ^[2]; Tan, M. H. Eileen ^[3]; Wang, Dongye ^[4]; Wu, Donghai ^[4]; Xu, H. Eric ^[5]; Melcher, Karsten ^[2]

Chinese Academy of Sciences, Guangdong (China); Univ. of Science and Technology of China, Anhui (China); Van Andel Research Institute, Grand Rapids, MI (United States)
Van Andel Research Institute, Grand Rapids, MI (United States)
Van Andel Research Institute, Grand Rapids, MI (United States); National Univ. of Singapore (Singapore)
Chinese Academy of Sciences, Guangdong (China)
Van Andel Research Institute, Grand Rapids, MI (United States); Chinese Academy of Sciences, Shanghai (China)

AMP-activated protein kinase (AMPK) is a central cellular energy sensor and regulator of energy homeostasis, and a promising drug target for the treatment of diabetes, obesity, and cancer. Here we present low-resolution crystal structures of the human α1β2γ1 holo-AMPK complex bound to its allosteric modulators AMP and the glycogen-mimic cyclodextrin, both in the phosphorylated (4.05 Å) and non-phosphorylated (4.60 Å) state. In addition, we have solved a 2.95 Å structure of the human kinase domain (KD) bound to the adjacent autoinhibitory domain (AID) and have performed extensive biochemical and mutational studies. Altogether, these studies illustrate an underlying mechanism of allosteric AMPK modulation by AMP and glycogen, whose binding changes the equilibria between alternate AID (AMP) and carbohydrate-binding module (glycogen) interactions.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1169343

Journal Information:: Cell Research, Vol. 25, Issue 1; ISSN 1001-0602

Publisher:: Shanghai Institutes for Biological SciencesCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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Cited by: 119 works

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References (59)

A gate–latch–lock mechanism for hormone signalling by abscisic acid receptors Melcher, Karsten; Ng, Ley-Moy; Zhou, X. Edward Nature, Vol. 462, Issue 7273 https://doi.org/10.1038/nature08613	journal	November 2009
AMP-Activated Protein Kinase: A Target for Drugs both Ancient and Modern Hardie, D. Grahame; Ross, Fiona A.; Hawley, Simon A. Chemistry & Biology, Vol. 19, Issue 10 https://doi.org/10.1016/j.chembiol.2012.08.019	journal	October 2012
AMPK β Subunit Targets Metabolic Stress Sensing to Glycogen Polekhina, Galina; Gupta, Abhilasha; Michell, Belinda J. Current Biology, Vol. 13, Issue 10 https://doi.org/10.1016/s0960-9822(03)00292-6	journal	May 2003
AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy Hardie, D. Grahame Nature Reviews Molecular Cell Biology, Vol. 8, Issue 10 https://doi.org/10.1038/nrm2249	journal	October 2007
Structural Insight into AMPK Regulation: ADP Comes into Play Jin, Xiangshu; Townley, Robert; Shapiro, Lawrence Structure, Vol. 15, Issue 10 https://doi.org/10.1016/j.str.2007.07.017	journal	October 2007
Structural basis of AMPK regulation by small molecule activators Xiao, Bing; Sanders, Matthew J.; Carmena, David Nature Communications, Vol. 4, Issue 1 https://doi.org/10.1038/ncomms4017	journal	December 2013
AMP-activated protein kinase undergoes nucleotide-dependent conformational changes Chen, Lei; Wang, Jue; Zhang, Yuan-Yuan Nature Structural & Molecular Biology, Vol. 19, Issue 7 https://doi.org/10.1038/nsmb.2319	journal	June 2012
Complexes between the LKB1 tumor suppressor, STRADα/β and MO25α/β are upstream kinases in the AMP-activated protein kinase cascade Hawley, Simon A.; Boudeau, Jérôme; Reid, Jennifer L. Journal of Biology, Vol. 2, Issue 4, p. 28 https://doi.org/10.1186/1475-4924-2-28	journal	January 2003
A plasmid expression system for quantitative in vivo biotinylation of thioredoxin fusion proteins in Escherichia coli Smith, P. A.; Tripp, B. C.; DiBlasio-Smith, E. A. Nucleic Acids Research, Vol. 26, Issue 6 https://doi.org/10.1093/nar/26.6.1414	journal	March 1998
Ca2+/calmodulin-dependent protein kinase kinase-β acts upstream of AMP-activated protein kinase in mammalian cells Woods, Angela; Dickerson, Kristina; Heath, Richard Cell Metabolism, Vol. 2, Issue 1 https://doi.org/10.1016/j.cmet.2005.06.005	journal	July 2005
Crystal structure of the heterotrimer core of Saccharomyces cerevisiae AMPK homologue SNF1 Amodeo, Gabriele A.; Rudolph, Michael J.; Tong, Liang Nature, Vol. 449, Issue 7161 https://doi.org/10.1038/nature06127	journal	September 2007
AMP Is a True Physiological Regulator of AMP-Activated Protein Kinase by Both Allosteric Activation and Enhancing Net Phosphorylation Gowans, Graeme J.; Hawley, Simon A.; Ross, Fiona A. Cell Metabolism, Vol. 18, Issue 4 https://doi.org/10.1016/j.cmet.2013.08.019	journal	October 2013
AMPK in Health and Disease Steinberg, Gregory R.; Kemp, Bruce E. Physiological Reviews, Vol. 89, Issue 3 https://doi.org/10.1152/physrev.00011.2008	journal	July 2009
Mammalian AMP-activated protein kinase: functional, heterotrimeric complexes by co-expression of subunits in Escherichia coli Neumann, Dietbert; Woods, Angela; Carling, David Protein Expression and Purification, Vol. 30, Issue 2 https://doi.org/10.1016/s1046-5928(03)00126-8	journal	August 2003
Structural basis for basal activity and autoactivation of abscisic acid (ABA) signaling SnRK2 kinases Ng, L. -M.; Soon, F. -F.; Zhou, X. E. Proceedings of the National Academy of Sciences, Vol. 108, Issue 52 https://doi.org/10.1073/pnas.1118651109	journal	December 2011
An antibody VH domain with a lox -Cre site integrated into its coding region: bacterial recombination within a single polypeptide chain Davies, Julian; Riechmann, Lutz FEBS Letters, Vol. 377, Issue 1 https://doi.org/10.1016/0014-5793(95)01313-X	journal	December 1995
Small Molecule Drug A-769662 and AMP Synergistically Activate Naive AMPK Independent of Upstream Kinase Signaling Scott, John W.; Ling, Naomi; Issa, Samah M. A. Chemistry & Biology, Vol. 21, Issue 5 https://doi.org/10.1016/j.chembiol.2014.03.006	journal	May 2014
AMP as a Low-Energy Charge Signal Autonomously Initiates Assembly of AXIN-AMPK-LKB1 Complex for AMPK Activation Zhang, Ya-Lin; Guo, Huiling; Zhang, Chen-Song Cell Metabolism, Vol. 18, Issue 4 https://doi.org/10.1016/j.cmet.2013.09.005	journal	October 2013
Functional Domains of the α1 Catalytic Subunit of the AMP-activated Protein Kinase Crute, Barbara E.; Seefeld, Kimberly; Gamble, James Journal of Biological Chemistry, Vol. 273, Issue 52 https://doi.org/10.1074/jbc.273.52.35347	journal	December 1998
AMPK Structure and Regulation from Three Angles Kemp, Bruce E.; Oakhill, Jonathan S.; Scott, John W. Structure, Vol. 15, Issue 10 https://doi.org/10.1016/j.str.2007.09.006	journal	October 2007
Coordinated regulation of AMPK activity by multiple elements in the α-subunit Xin, Feng-Jiao; Wang, Jue; Zhao, Rong-Qing Cell Research, Vol. 23, Issue 10 https://doi.org/10.1038/cr.2013.121	journal	September 2013
Branching out on AMPK Regulation Carling, David Cell Metabolism, Vol. 9, Issue 1 https://doi.org/10.1016/j.cmet.2008.12.007	journal	January 2009
-Subunit myristoylation is the gatekeeper for initiating metabolic stress sensing by AMP-activated protein kinase (AMPK) Oakhill, J. S.; Chen, Z. -P.; Scott, J. W. Proceedings of the National Academy of Sciences, Vol. 107, Issue 45 https://doi.org/10.1073/pnas.1009705107	journal	October 2010
Calmodulin-dependent protein kinase kinase-β is an alternative upstream kinase for AMP-activated protein kinase Hawley, Simon A.; Pan, David A.; Mustard, Kirsty J. Cell Metabolism, Vol. 2, Issue 1 https://doi.org/10.1016/j.cmet.2005.05.009	journal	July 2005
Coot model-building tools for molecular graphics Emsley, Paul; Cowtan, Kevin Acta Crystallographica Section D Biological Crystallography, Vol. 60, Issue 12, p. 2126-2132 https://doi.org/10.1107/S0907444904019158	journal	November 2004
Conserved α-Helix Acts as Autoinhibitory Sequence in AMP-activated Protein Kinase α Subunits Pang, Tao; Xiong, Bing; Li, Jing-Ya Journal of Biological Chemistry, Vol. 282, Issue 1 https://doi.org/10.1074/jbc.M605790200	journal	November 2006
Structural Basis for AMPK Activation: Natural and Synthetic Ligands Regulate Kinase Activity from Opposite Poles by Different Molecular Mechanisms Calabrese, Matthew F.; Rajamohan, Francis; Harris, Melissa S. Structure, Vol. 22, Issue 8 https://doi.org/10.1016/j.str.2014.06.009	journal	August 2014
Structural Basis for Glycogen Recognition by AMP-Activated Protein Kinase Polekhina, Galina; Gupta, Abhilasha; van Denderen, Bryce J. W. Structure, Vol. 13, Issue 10 https://doi.org/10.1016/j.str.2005.07.008	journal	October 2005
AMPK β subunits display isoform specific affinities for carbohydrates Koay, Ann; Woodcroft, Ben; Petrie, Emma J. FEBS Letters, Vol. 584, Issue 15 https://doi.org/10.1016/j.febslet.2010.07.015	journal	July 2010
Structure of mammalian AMPK and its regulation by ADP Xiao, Bing; Sanders, Matthew J.; Underwood, Elizabeth Nature, Vol. 472, Issue 7342 https://doi.org/10.1038/nature09932	journal	March 2011
Determining kinetics and affinities of protein interactions using a parallel real-time label-free biosensor, the Octet Abdiche, Yasmina; Malashock, Dan; Pinkerton, Alanna Analytical Biochemistry, Vol. 377, Issue 2 https://doi.org/10.1016/j.ab.2008.03.035	journal	June 2008
Conserved regulatory elements in AMPK Chen, Lei; Xin, Feng-Jiao; Wang, Jue Nature, Vol. 498, Issue 7453 https://doi.org/10.1038/nature12189	journal	June 2013
The Ca ²⁺ /Calmodulin-dependent Protein Kinase Kinases Are AMP-activated Protein Kinase Kinases Hurley, Rebecca L.; Anderson, Kristin A.; Franzone, Jeanne M. Journal of Biological Chemistry, Vol. 280, Issue 32 https://doi.org/10.1074/jbc.m503824200	journal	June 2005
LKB1 Is the Upstream Kinase in the AMP-Activated Protein Kinase Cascade Woods, Angela; Johnstone, Stephen R.; Dickerson, Kristina Current Biology, Vol. 13, Issue 22 https://doi.org/10.1016/j.cub.2003.10.031	journal	November 2003
Identification and characterization of a small molecule AMPK activator that treats key components of type 2 diabetes and the metabolic syndrome Cool, Barbara; Zinker, Bradley; Chiou, William Cell Metabolism, Vol. 3, Issue 6 https://doi.org/10.1016/j.cmet.2006.05.005	journal	June 2006
AMPK: a nutrient and energy sensor that maintains energy homeostasis Hardie, D. Grahame; Ross, Fiona A.; Hawley, Simon A. Nature Reviews Molecular Cell Biology, Vol. 13, Issue 4 https://doi.org/10.1038/nrm3311	journal	March 2012
Inhibition of AMPK Catabolic Action by GSK3 Suzuki, Tsukasa; Bridges, Dave; Nakada, Daisuke Molecular Cell, Vol. 50, Issue 3 https://doi.org/10.1016/j.molcel.2013.03.022	journal	May 2013
A new protein kinase cascade Hardie, D. Grahame Nature Reviews Molecular Cell Biology, Vol. 15, Issue 4 https://doi.org/10.1038/nrm3771	journal	March 2014
The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress Shaw, R. J.; Kosmatka, M.; Bardeesy, N. Proceedings of the National Academy of Sciences, Vol. 101, Issue 10 https://doi.org/10.1073/pnas.0308061100	journal	February 2004
Bypassing AMPK Phosphorylation Viollet, Benoit; Foretz, Marc; Schlattner, Uwe Chemistry & Biology, Vol. 21, Issue 5 https://doi.org/10.1016/j.chembiol.2014.05.003	journal	May 2014
Iterative model building, structure refinement and density modification with the PHENIX AutoBuild wizard Terwilliger, Thomas C.; Grosse-Kunstleve, Ralf W.; Afonine, Pavel V. Acta Crystallographica Section D Biological Crystallography, Vol. 64, Issue 1 https://doi.org/10.1107/S090744490705024X	journal	December 2007
Crystallography & NMR System: A New Software Suite for Macromolecular Structure Determination Brünger, A. T.; Adams, P. D.; Clore, G. M. Acta Crystallographica Section D Biological Crystallography, Vol. 54, Issue 5 https://doi.org/10.1107/S0907444998003254	journal	September 1998
Conformational exchange in the potassium channel blocker ShK Iwakawa, Naoto; Baxter, Nicola J.; Wai, Dorothy C. C. Scientific Reports, Vol. 9, Issue 1 https://doi.org/10.1038/s41598-019-55806-3	journal	December 2019
The AMPK signalling pathway coordinates cell growth, autophagy and metabolism Mihaylova, Maria M.; Shaw, Reuben J. Nature Cell Biology, Vol. 13, Issue 9 https://doi.org/10.1038/ncb2329	journal	September 2011
Structural insight into the autoinhibition mechanism of AMP-activated protein kinase Chen, Lei; Jiao, Zhi-Hao; Zheng, Li-Sha Nature, Vol. 459, Issue 7250 https://doi.org/10.1038/nature08075	journal	May 2009
Efficient Rebuilding of Protein Structures Kleywegt, G. J.; Jones, T. A. Acta Crystallographica Section D Biological Crystallography, Vol. 52, Issue 4 https://doi.org/10.1107/S0907444996001783	journal	July 1996
The Glycogen-Binding Domain on the AMPK β Subunit Allows the Kinase to Act as a Glycogen Sensor McBride, Andrew; Ghilagaber, Stephanos; Nikolaev, Andrei Cell Metabolism, Vol. 9, Issue 1 https://doi.org/10.1016/j.cmet.2008.11.008	journal	January 2009
Structural Properties of AMP-activated Protein Kinase Riek, Uwe; Scholz, Roland; Konarev, Peter Journal of Biological Chemistry, Vol. 283, Issue 26 https://doi.org/10.1074/jbc.M708379200	journal	March 2008
Surface comparison of active and inactive protein kinases identifies a conserved activation mechanism Kornev, A. P.; Haste, N. M.; Taylor, S. S. Proceedings of the National Academy of Sciences, Vol. 103, Issue 47 https://doi.org/10.1073/pnas.0607656103	journal	November 2006
The α1 and α2 isoforms of the AMP-activated protein kinase have similar activities in rat liver but exhibit differences in substrate specificity in vitro Woods, Angela; Salt, Ian; Scott, James FEBS Letters, Vol. 397, Issue 2-3 https://doi.org/10.1016/S0014-5793(96)01209-4	journal	November 1996
AMPK Is a Direct Adenylate Charge-Regulated Protein Kinase Oakhill, J. S.; Steel, R.; Chen, Z. -P. Science, Vol. 332, Issue 6036 https://doi.org/10.1126/science.1200094	journal	June 2011
Purification and characterization of the AMP-activated protein kinase. Copurification of acetyl-CoA carboxylase kinase and 3-hydroxy-3-methylglutaryl-CoA reductase kinase activities Carling, David; Clarke, Paul R.; Zammit, Victor A. European Journal of Biochemistry, Vol. 186, Issue 1-2 https://doi.org/10.1111/j.1432-1033.1989.tb15186.x	journal	December 1989
Phosphorylation by Akt within the ST loop of AMPK-α1 down-regulates its activation in tumour cells Hawley, Simon A.; Ross, Fiona A.; Gowans, Graeme J. Biochemical Journal, Vol. 459, Issue 2 https://doi.org/10.1042/BJ20131344	journal	March 2014
Iterative model building, structure refinement and density modification with the PHENIX AutoBuild wizard. Terwilliger, Thomas C.; Grosse-Kunstleve, Ralf W.; Afonine, Pavel V. International Union of Crystallography (IUCr) https://doi.org/10.17863/cam.52329	journalarticle	January 2008
Post-translational modifications of the β-1 subunit of AMP-activated protein kinase affect enzyme activity and cellular localization Warden, Scott M.; Richardson, Christine; O'Donnell, John Biochemical Journal, Vol. 354, Issue 2 https://doi.org/10.1042/bj3540275	journal	February 2001
Post-translational modifications of the β-1 subunit of AMP-activated protein kinase affect enzyme activity and cellular localization Warden, Scott M.; Richardson, Christine; O’DONNELL Jr, John Biochemical Journal, Vol. 354, Issue 2 https://doi.org/10.1042/0264-6021:3540275	journal	March 2001
Multiparametric scaling of diffraction intensities Otwinowski, Zbyszek; Borek, Dominika; Majewski, Wladyslaw Acta Crystallographica Section A Foundations of Crystallography, Vol. 59, Issue 3 https://doi.org/10.1107/S0108767303005488	journal	April 2003
Phaser crystallographic software McCoy, Airlie J.; Grosse-Kunstleve, Ralf W.; Adams, Paul D. Journal of Applied Crystallography, Vol. 40, Issue 4 https://doi.org/10.1107/S0021889807021206	journal	July 2007
Regulation of rat liver acetyl-CoA carboxylase. Regulation of phosphorylation and inactivation of acetyl-CoA carboxylase by the adenylate energy charge. Yeh, L. A.; Lee, K. H.; Kim, K. H. Journal of Biological Chemistry, Vol. 255, Issue 6 https://doi.org/10.1016/S0021-9258(19)85891-X	journal	March 1980

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AMPK
adenine nucleotides
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diabetes

Title: Structural basis of AMPK regulation by adenine nucleotides and glycogen

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