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 JBM  Vol.5 No.8 , August 2017
Structural Basis for the Interaction of 14-3-3β with Tricarboxylic Acid Cycle Intermediate Malate
Abstract: The protein family of 14-3-3(s) has risen to a position of higher importance as an adaptor protein in cell biology. The seven highly conserved human 14-3-3 proteins coordinate diverse cellular processes including apoptosis, DNA damage response, protein trafficking, and others. In liver hepatocytes, 14-3-3β binds to Ser196-phosphorilated glucose-responsive carbohydrate response element-binding protein (ChREBP) to inhibit converting excess carbohydrate to fat by regulating the nuclear/cytosol trafficking of ChREBP. Here, we report X-ray crystal structures of homodimeric mammalian 14-3-3β in its apo, Malate-bound forms. The determined apo structure was captured with one monomer in the closed state, whereas the other one had an open conformation. Strikingly, 14-3-3β binds Malate dynamically with a double-closed state, which is distinct from all previously characterized 14-3-3(s) and target ligand-binding modes. Malate docks into a first-time observed cofactor pocket located at the concaved interface of 14-3-3β helices α2, α3, α4 through mainly electrostatic and hydrogen interactions. Such a Tricarboxylic Acid Cycle intermediate Malate bond model might offer a new approach to further analyze insulin-independent 14-3-3/ChREBP pathway of de novo fat synthesis in the liver.
Cite this paper: Hou, Z. , Su, L. , Liu, X. (2017) Structural Basis for the Interaction of 14-3-3β with Tricarboxylic Acid Cycle Intermediate Malate. Journal of Biosciences and Medicines, 5, 36-47. doi: 10.4236/jbm.2017.58003.
References

[1]   Bridges, D. and Moorhead, G.B. (2005) 14-3-3 Proteins: A Number of Functions for a Numbered Protein. Science's STKE: Signal Transduction Knowledge Environment, 2005, re10.
https://doi.org/10.1126/stke.2962005re10

[2]   Joo, Y., Schumacher, B., Landrieu, I., Bartel, M., Smet-Nocca, C., Jang, A., Choi, H.S., Jeon, N.L., Chang, K.A., Kim, H.S., Ottmann, C. and Suh, Y.H. (2015) Involvement of 14-3-3 in Tubulin Instability and Impaired Axon Development Is Mediated by Tau. FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology, 29, 4133-4144.
https://doi.org/10.1096/fj.14-265009

[3]   Rosenquist, M., Sehnke, P., Ferl, R.J., Sommarin, M. and Larsson, C. (2000) Evolution of the 14-3-3 Protein Family: Does the Large Number of Isoforms in Multicellular Organisms Reflect Functional Specificity? Journal of Molecular Evolution, 51, 446-458.
https://doi.org/10.1007/s002390010107

[4]   Siles-Lucas Mdel, M. and Gottstein, B. (2003) The 14-3-3 Protein: A Key Molecule in Parasites as in Other Organisms. Trends in Parasitology, 19, 575-581.
https://doi.org/10.1016/j.pt.2003.10.003

[5]   Coblitz, B., Wu, M., Shikano, S. and Li, M. (2006) C-Terminal Binding: An Expanded Repertoire and Function of 14-3-3 Proteins. FEBS Letters, 580, 1531-1535.
https://doi.org/10.1016/j.febslet.2006.02.014

[6]   Ge, Q., Huang, N., Wynn, R.M., Li, Y., Du, X., Miller, B., Zhang, H. and Uyeda, K. (2012) Structural Characterization of a Unique Interface between Carbohydrate Response Element-Binding Protein (ChREBP) and 14-3-3βProtein. The Journal of Biological Chemistry, 287, 41914-41921.
https://doi.org/10.1074/jbc.M112.418855

[7]   Zhai, J., Lin, H., Shamim, M., Schlaepfer, W.W. and Canete-Soler, R. (2001) Identification of a Novel Interaction of 14-3-3 with p190RhoGEF. The Journal of Biological Chemistry, 276, 41318-41324.
https://doi.org/10.1074/jbc.M107709200

[8]   Sato, S., Jung, H., Nakagawa, T., Pawlosky, R., Takeshima, T., Lee, W.R., Sakiyama, H., Laxman, S., Wynn, R.M., Tu, B.P., MacMillan, J.B., De Brabander, J.K., Veech, R.L. and Uyeda, K. (2016) Metabolite Regulation of Nuclear Localization of Carbohydrate-Response Element-binding Protein (ChREBP): Role of Amp as An Allosteric Inhibitor. The Journal of Biological Chemistry, 291, 10515-10527.
https://doi.org/10.1074/jbc.M115.708982

[9]   Dougherty, M.K. and Morrison, D.K. (2004) Unlocking the Code of 14-3-3. Journal of Cell Science, 117, 1875-1884.
https://doi.org/10.1242/jcs.01171

[10]   Obsilova, V., Kopecka, M., Kosek, D., Kacirova, M., Kylarova, S., Rezabkova, L. and Obsil, T. (2014) Mechanisms of the 14-3-3 Protein Function: Regulation of Protein Function through Conformational Modulation. Physiological Research, 63, S155-S164.

[11]   Yaffe, M.B. (2002) How Do 14-3-3 Proteins Work? Gatekeeper Phosphorylation and the Molecular Anvil Hypothesis. FEBS Letters, 513, 53-57.
https://doi.org/10.1016/S0014-5793(01)03288-4

[12]   Jerome, M. and Paudel, H.K. (2014) 14-3-3ΔRegulates Nuclear Trafficking of Protein Phosphatase 1alpha (PP1α) in HEK-293 Cells. Archives of Biochemistry and Biophysics, 558, 28-35.
https://doi.org/10.1016/j.abb.2014.06.012

[13]   Milroy, L.G., Bartel, M., Henen, M.A., Leysen, S., Adriaans, J.M., Brunsveld, L., Landrieu, I. and Ottmann, C. (2015) Stabilizer-Guided Inhibition of Protein-Protein Interactions. Angewandte Chemie, 54, 15720-15724.
https://doi.org/10.1002/anie.201507976

[14]   Urano, T., Saito, T., Tsukui, T., Fujita, M., Hosoi, T., Muramatsu, M., Ouchi, Y., and Inoue, S. (2002) Efp Targets 14-3-3σ for Proteolysis and Promotes Breast Tumour Growth. Nature, 417, 871-875.
https://doi.org/10.1038/nature00826

[15]   Sun, N., Wu, Y., Huang, B., Liu, Q., Dong, Y., Ding, J. and Liu, Y. (2015) Decreased Expression of 14-3-3σ, An Early Event of Malignant Transformation of Respiratory Epithelium, Also Facilitates Progression of Squamous Cell Lung Cancer. Thoracic Cancer, 6, 715-721.
https://doi.org/10.1111/1759-7714.12246

[16]   Dutta, D., Ali, N., Banerjee, E., Singh, R., Naskar, A., Paidi, R.K. and Mohanakumar, K.P. (2017) Low Levels of Prohibitin in Substantia Nigra Makes Dopaminergic Neurons Vulnerable in Parkinson’s Disease. Molecular Neurobiology, 54, 1-18.

[17]   Wiltfang, J., Otto, M., Baxter, H.C., Bodemer, M., Steinacker, P., Bahn, E., Zerr, I., Kornhuber, J., Kretzschmar, H.A., Poser, S., Ruther, E. and Aitken, A. (1999) Isoform Pattern of 14-3-3 Proteins in the Cerebrospinal Fluid of Patients with Creutzfeldt-Jakob Disease. Journal of Neurochemistry, 73, 2485-2490.
https://doi.org/10.1046/j.1471-4159.1999.0732485.x

[18]   Sakiyama, H., Wynn, R.M., Lee, W.R., Fukasawa, M., Mizuguchi, H., Gardner, K.H., Repa, J.J. and Uyeda, K. (2008) Regulation of Nuclear Import/Export of Carbohydrate Response Element-Binding Protein (ChREBP): Interaction of an Alpha-Helix of ChREBP with the 14-3-3 Proteins and Regulation by Phosphorylation. The Journal of Biological Chemistry, 283, 24899-24908.
https://doi.org/10.1074/jbc.M804308200

[19]   Kabashima, T., Kawaguchi, T., Wadzinski, B.E. and Uyeda, K. (2003) Xylulose 5-Phosphate Mediates Glucose-Induced Lipogenesis by Xylulose 5-Phosphate-Ac- tivated Protein Phosphatase in Rat Liver. Pro-ceedings of the National Academy of Sciences of the United States of America, 100, 5107-5112.
https://doi.org/10.1073/pnas.0730817100

[20]   Sheffield, P., Garrard, S. and Derewenda, Z. (1999) Overcoming Expression and Purification Problems of RhoGDI Using a Family of “Parallel” Expression Vectors. Protein Expression and Purification, 15, 34-39.
https://doi.org/10.1006/prep.1998.1003

[21]   Otwinowski, Z. and Minor, W. (1997) Processing of X-Ray Diffraction Data Collected in Oscillation Mode. Methods in Enzymology, 276, 307-326.
https://doi.org/10.1016/S0076-6879(97)76066-X

[22]   Adams, P.D., Afonine, P.V., Bunkoczi, G., Chen, V.B., Davis, I.W., Echols, N., Headd, J.J., Hung, L.W., Kapral, G.J., Grosse-Kunstleve, R.W., McCoy, A.J., Moriarty, N.W., Oeffner, R., Read, R.J., Richardson, D.C., Richardson, J.S., Terwilliger, T.C. and Zwart, P.H. (2010) PHENIX: A Comprehensive Python-Based System for Macromolecular Structure Solution. Acta Crystallographica Section D, Biological Crystallography, 66, 213-221.
https://doi.org/10.1107/S0907444909052925

[23]   Emsley, P., Lohkamp, B., Scott, W.G. and Cowtan, K. (2010) Features and Development of Coot. Acta Crystallographica Section D, 66, 486-501.
https://doi.org/10.1107/S0907444910007493

[24]   Bailey, S. (1994) The Ccp4 Suite-Programs for Protein Crystallography. Acta Crystallographica D, 50, 760-763.
https://doi.org/10.1107/S0907444994003112

[25]   Berman, H.M., Westbrook, J., Feng, Z., Gilliland, G., Bhat, T.N., Weissig, H., Shindyalov, I.N. and Bourne, P.E. (2000) The Protein Data Bank. Nucleic Acids Research, 28, 235-242.
https://doi.org/10.1093/nar/28.1.235

[26]   Xiao, B., Smerdon, S.J., Jones, D.H., Dodson, G.G., Soneji, Y., Aitken, A. and Gamblin, S.J. (1995) Structure of a 14-3-3 Protein and Implications for Coordination of Multiple Signalling Pathways. Nature, 376, 188-191.
https://doi.org/10.1038/376188a0

[27]   Potterton, L., McNicholas, S., Krissinel, E., Gruber, J., Cowtan, K., Emsley, P., Murshudov, G.N., Cohen, S., Perrakis, A. and Noble, M. (2004) Developments in the CCP4 Molecular-Graphics Project. Acta Crystallographica D, 60, 2288-2294.
https://doi.org/10.1107/S0907444904023716

[28]   MacDonald, M.J. (1995) Feasibility of a Mitochondrial Pyruvate Malate Shuttle in Pancreatic Islets. Further Implication of Cytosolic NADPH in Insulin Secretion. The Journal of Biological Chemistry, 270, 20051-20058.

[29]   Ferre, P. and Foufelle, F. (2007) SREBP-1c Transcription Factor and Lipid Homeostasis: Clinical Perspective. Hormone Research, 68, 72-82.
https://doi.org/10.1159/000100426

[30]   Davis, I.W., Murray, L.W., Richardson, J.S. and Richardson, D.C. (2004) MOLPROBITY: Structure Validation and All-Atom Contact Analysis for Nucleic Acids and Their Complexes. Nucleic Acids Research, 32, W615-W619.
https://doi.org/10.1093/nar/gkh398

[31]   Nakagawa, T., Ge, Q., Pawlosky, R., Wynn, R.M., Veech, R.L. and Uyeda, K. (2013) Metabolite Regulation of Nucleo-Cytosolic Trafficking of Carbohydrate Response Element-Binding Protein (ChREBP): Role of Ketone Bodies. The Journal of Biological Chemistry, 288, 28358-28367.
https://doi.org/10.1074/jbc.M113.498550

[32]   Dentin, R., Tomas-Cobos, L., Foufelle, F., Leopold, J., Girard, J., Postic, C. and Ferre, P. (2012) Glucose 6-Phosphate, Rather than Xylulose 5-Phosphate, Is Required for the Activation of ChREBP in Response to Glucose in the Liver. Journal of Hepatology, 56, 199-209.
https://doi.org/10.1016/j.jhep.2011.07.019

 
 
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