| Structural highlights
2qlv is a 6 chain structure with sequence from Atcc 18824. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Gene: | SNF1, CAT1, CCR1, GLC2, PAS14 (ATCC 18824), SIP2, SPM2 (ATCC 18824), SNF4, CAT3 (ATCC 18824) |
| Activity: | Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[SNF1_YEAST] Essential for release from glucose repression. It interacts and has functional relationship to the regulatory protein SNF4. Could phosphorylate CAT8. Phosphorylates histone H3 to form H3S10ph, which promotes H3K14ac formation, and which is required for transcriptional activation through TBP recruitment to the promoters.[1] [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.[2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [SIP2_YEAST] Beta subunit of the SNF1 kinase complex, which is required for transcriptional, metabolic, and developmental adaptations in response to glucose limitation. Has a structural role, mediating heterotrimer formation, and a regulatory role, defining carbon source-regulated subcellular location and substrate specificity of the SNF1 kinase complex. Involved in the regulation of aging. Acts as a negative regulator of nuclear SNF1 activity in young cells by sequestering its activating gamma subunit at the plasma membrane.[20] [21]
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 and is an attractive target for drug discovery against diabetes, obesity and other diseases. The AMPK homologue in Saccharomyces cerevisiae, known as SNF1, is essential for responses to glucose starvation as well as for other cellular processes, although SNF1 seems to be activated by a ligand other than AMP. Here we report the crystal structure at 2.6 A resolution of the heterotrimer core of SNF1. The ligand-binding site in the gamma-subunit (Snf4) has clear structural differences from that of the Schizosaccharomyces pombe enzyme, although our crystallographic data indicate that AMP can also bind to Snf4. The glycogen-binding domain in the beta-subunit (Sip2) interacts with Snf4 in the heterotrimer but should still be able to bind carbohydrates. Our structure is supported by a large body of biochemical and genetic data on this complex. Most significantly, the structure reveals that part of the regulatory sequence in the alpha-subunit (Snf1) is sequestered by Snf4, demonstrating a direct interaction between the alpha- and gamma-subunits and indicating that our structure may represent the heterotrimer core of SNF1 in its activated state.
Crystal structure of the heterotrimer core of Saccharomyces cerevisiae AMPK homologue SNF1.,Amodeo GA, Rudolph MJ, Tong L Nature. 2007 Sep 27;449(7161):492-5. Epub 2007 Sep 12. PMID:17851534[22]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lo WS, Gamache ER, Henry KW, Yang D, Pillus L, Berger SL. Histone H3 phosphorylation can promote TBP recruitment through distinct promoter-specific mechanisms. EMBO J. 2005 Mar 9;24(5):997-1008. Epub 2005 Feb 17. PMID:15719021 doi:7600577
- ↑ Aon MA, Cortassa S. Catabolite repression mutants of Saccharomyces cerevisiae show altered fermentative metabolism as well as cell cycle behavior in glucose-limited chemostat cultures. Biotechnol Bioeng. 1998 Jul 20;59(2):203-13. PMID:10099331
- ↑ 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
- ↑ Nath N, McCartney RR, Schmidt MC. Purification and characterization of Snf1 kinase complexes containing a defined Beta subunit composition. J Biol Chem. 2002 Dec 27;277(52):50403-8. Epub 2002 Oct 21. PMID:12393914 doi:http://dx.doi.org/10.1074/jbc.M207058200
- ↑ 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
- ↑ Celenza JL, Carlson M. Mutational analysis of the Saccharomyces cerevisiae SNF1 protein kinase and evidence for functional interaction with the SNF4 protein. Mol Cell Biol. 1989 Nov;9(11):5034-44. PMID:2557546
- ↑ 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
- ↑ Entian KD, Zimmermann FK. New genes involved in carbon catabolite repression and derepression in the yeast Saccharomyces cerevisiae. J Bacteriol. 1982 Sep;151(3):1123-8. PMID:7050076
- ↑ Fernandez E, Fernandez M, Moreno F, Rodicio R. Transcriptional regulation of the isocitrate lyase encoding gene in Saccharomyces cerevisiae. FEBS Lett. 1993 Nov 1;333(3):238-42. PMID:8224185
- ↑ 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
- ↑ Schmidt MC, McCartney RR. beta-subunits of Snf1 kinase are required for kinase function and substrate definition. EMBO J. 2000 Sep 15;19(18):4936-43. PMID:10990457 doi:http://dx.doi.org/10.1093/emboj/19.18.4936
- ↑ Lin SS, Manchester JK, Gordon JI. Sip2, an N-myristoylated beta subunit of Snf1 kinase, regulates aging in Saccharomyces cerevisiae by affecting cellular histone kinase activity, recombination at rDNA loci, and silencing. J Biol Chem. 2003 Apr 11;278(15):13390-7. Epub 2003 Jan 31. PMID:12562756 doi:http://dx.doi.org/10.1074/jbc.M212818200
- ↑ Amodeo GA, Rudolph MJ, Tong L. Crystal structure of the heterotrimer core of Saccharomyces cerevisiae AMPK homologue SNF1. Nature. 2007 Sep 27;449(7161):492-5. Epub 2007 Sep 12. PMID:17851534 doi:http://dx.doi.org/10.1038/nature06127
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