| Structural highlights
Function
AAKG_YEAST Adenine nucleotides-binding subunit gamma of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Gamma non-catalytic subunit mediates binding to AMP, ADP and ATP, leading to activate or inhibit AMPK: AMP-binding results in allosteric activation of alpha catalytic subunit (SNF1) both by inducing phosphorylation and preventing dephosphorylation of catalytic subunits.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
AMP-activated protein kinase (AMPK) is a central regulator of energy homeostasis in mammals. AMP is believed to control the activity of AMPK by binding to the gamma subunit of this heterotrimeric enzyme. This subunit contains two Bateman domains, each of which is composed of a tandem pair of cystathionine beta-synthase (CBS) motifs. No structural information is currently available on this subunit, and the molecular basis for its interactions with AMP is not well understood. We report here the crystal structure at 1.9 Angstrom resolution of the Bateman2 domain of Snf4, the gamma subunit of the yeast ortholog of AMPK. The structure revealed a dimer of the Bateman2 domain, and this dimerization is supported by our light-scattering, mutagenesis, and biochemical studies. There is a prominent pocket at the center of this dimer, and most of the disease-causing mutations are located in or near this pocket.
Structure of the Bateman2 domain of yeast Snf4: dimeric association and relevance for AMP binding.,Rudolph MJ, Amodeo GA, Iram SH, Hong SP, Pirino G, Carlson M, Tong L Structure. 2007 Jan;15(1):65-74. PMID:17223533[19]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
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- ↑ Shirra MK, Arndt KM. Evidence for the involvement of the Glc7-Reg1 phosphatase and the Snf1-Snf4 kinase in the regulation of INO1 transcription in Saccharomyces cerevisiae. Genetics. 1999 May;152(1):73-87. PMID:10224244
- ↑ McCartney RR, Schmidt MC. Regulation of Snf1 kinase. Activation requires phosphorylation of threonine 210 by an upstream kinase as well as a distinct step mediated by the Snf4 subunit. J Biol Chem. 2001 Sep 28;276(39):36460-6. Epub 2001 Aug 2. PMID:11486005 doi:http://dx.doi.org/10.1074/jbc.M104418200
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- ↑ Haurie V, Boucherie H, Sagliocco F. The Snf1 protein kinase controls the induction of genes of the iron uptake pathway at the diauxic shift in Saccharomyces cerevisiae. J Biol Chem. 2003 Nov 14;278(46):45391-6. Epub 2003 Sep 5. PMID:12960168 doi:http://dx.doi.org/10.1074/jbc.M307447200
- ↑ Estruch F, Treitel MA, Yang X, Carlson M. N-terminal mutations modulate yeast SNF1 protein kinase function. Genetics. 1992 Nov;132(3):639-50. PMID:1468623
- ↑ Momcilovic M, Iram SH, Liu Y, Carlson M. Roles of the glycogen-binding domain and Snf4 in glucose inhibition of SNF1 protein kinase. J Biol Chem. 2008 Jul 11;283(28):19521-9. doi: 10.1074/jbc.M803624200. Epub 2008 , May 12. PMID:18474591 doi:http://dx.doi.org/10.1074/jbc.M803624200
- ↑ Arguelles JC, Mbonyi K, Van Aelst L, Vanhalewyn M, Jans AW, Thevelein JM. Absence of glucose-induced cAMP signaling in the Saccharomyces cerevisiae mutants cat1 and cat3 which are deficient in derepression of glucose-repressible proteins. Arch Microbiol. 1990;154(2):199-205. PMID:2169717
- ↑ Mayer FV, Heath R, Underwood E, Sanders MJ, Carmena D, McCartney RR, Leiper FC, Xiao B, Jing C, Walker PA, Haire LF, Ogrodowicz R, Martin SR, Schmidt MC, Gamblin SJ, Carling D. ADP Regulates SNF1, the Saccharomyces cerevisiae Homolog of AMP-Activated Protein Kinase. Cell Metab. 2011 Nov 2;14(5):707-14. Epub 2011 Oct 20. PMID:22019086 doi:10.1016/j.cmet.2011.09.009
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- ↑ Bisson LF. High-affinity glucose transport in Saccharomyces cerevisiae is under general glucose repression control. J Bacteriol. 1988 Oct;170(10):4838-45. PMID:3049551
- ↑ Sarokin L, Carlson M. Upstream region of the SUC2 gene confers regulated expression to a heterologous gene in Saccharomyces cerevisiae. Mol Cell Biol. 1985 Oct;5(10):2521-6. PMID:3939253
- ↑ Neigeborn L, Carlson M. Genes affecting the regulation of SUC2 gene expression by glucose repression in Saccharomyces cerevisiae. Genetics. 1984 Dec;108(4):845-58. PMID:6392017
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- ↑ Blazquez MA, Gancedo C. Mode of action of the qcr9 and cat3 mutations in restoring the ability of Saccharomyces cerevisiae tps1 mutants to grow on glucose. Mol Gen Genet. 1995 Dec 20;249(6):655-64. PMID:8544831
- ↑ Jiang R, Carlson M. Glucose regulates protein interactions within the yeast SNF1 protein kinase complex. Genes Dev. 1996 Dec 15;10(24):3105-15. PMID:8985180
- ↑ Ludin K, Jiang R, Carlson M. Glucose-regulated interaction of a regulatory subunit of protein phosphatase 1 with the Snf1 protein kinase in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 1998 May 26;95(11):6245-50. PMID:9600950
- ↑ Rudolph MJ, Amodeo GA, Iram SH, Hong SP, Pirino G, Carlson M, Tong L. Structure of the Bateman2 domain of yeast Snf4: dimeric association and relevance for AMP binding. Structure. 2007 Jan;15(1):65-74. PMID:17223533 doi:http://dx.doi.org/10.1016/j.str.2006.11.014
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