研究领域
Biophysical Chemistry/Chemical Biology/Physical Chemistry
The main focus of our research is to use NMR and other biophysical techniques to elucidate the molecular structure and function of neuronal calcium sensor proteins that regulate phototransduction in vision and other signal transduction processes. We're currently studying retinal recoverin, a calcium sensor in vision, and the guanylate cyclase activating proteins (GCAPs), implicated in autosomal dominant cone dystrophy. Our studies also include neuronal homologs, such as the DREAM protein in the brain that serves as a transcriptional repressor for pain modulation as well as a sublcass of EF-hand proteins (CaBPs) that modulate the activity of neuronal Ca2+ channels. This emerging family of proteins is important for signal transduction generally because Ca2+-induced conformational changes in these proteins control their cellular location and capacity to interact with membrane-bound targets and/or DNA elements. The long-term goal of our work is to develop an atomic-level understanding of how neuronal calcium sensor proteins operate in signal transduction and disease processes.
近期论文
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Xu, X., Ishima, R. and Ames, J.B. (2010) Conformational Dynamics of Recoverin�s Ca2+-myristoyl Switch. Biochemistry, submitted.
Kohler AC, Gae DD, Richley MA, Stoll S, Gunn A, Lim S, Martin SS, Doukov TI, Britt RD, Ames JB, Lagarias JC, Fisher AJ (2010) Structural basis for hydration dynamics in radical stabilization of bilin reductase mutants. Biochemistry, 49:6206-6218.
Park S., Li C., Ames J.B. (2010) (1)H, (15)N, and (13)C chemical shift assignments of calcium-binding protein 1 with Ca(2+) bound at EF1, EF3 and EF4. Biomol. NMR Assignments, in press.
Zhang, Y., Stadler, S. and Ames J.B. (2010) Backbone Chemical Shift Assignments of Mouse HOXA13 DNA Binding Domain Bound to Duplex DNA. Biomol. NMR Assignments, 4:97-99.
Xu, X., Li, Y., Xu, W., Rayo, J., Ishida, Y., Leal, W.S. and Ames, J.B. (2010) NMR Structure of Navel Orangeworm Moth Pheromone Binding Protein (AtraPBP1): Implications for pH-Sensitive Pheromone Detection. Biochemistry, 49:1469-1476..
Valentine, K.G., Summers, M.F., Xu, X., Ames, J.B and Wand, J.S. (2010) Reverse Micelle Encapsulation of Membrane Anchored Proteins for Solution NMR Studies. Structure, 18: 9-16.
Hamasaki, N. and Ames J.B. (2010) Neuronal Calcium Sensor-1 (Ncs1p) is Upregulated by Calcineurin to Promote Ca2+ Tolerance in Fission Yeast. J. Biol. Chem., 285: 4405-4414.
Schenauer, M.R., Meissen, J.K., Seo, Y., Ames, J.B. and Leary, J.A. (2009) Heparan Sulfate Separation, Sequencing, and Isomeric Differentiation: Ion Mobility Spectrometry Reveals Specific Iduronic and Glucuronic Acid-Containing Hexasaccharides. Analytical Chemistry, 81: 10179-85.
Lim, S. and Ames J.B. (2009) 1H, 15N, and 13C Chemical Shift Assignments of Neuronal Calcium Sensor-1 homolog from fission yeast. Biomol. NMR Assignments, 3: 269-271.
Zhang, Y., Stadler, S. and Ames J.B. (2009) 1H, 15N, and 13C Chemical Shift Assignments of HOXA13 DNA Binding Domain. Biomol. NMR Assignments, 3: 199-201.
Xu, X., Li, Y., Ishida, Y., Leal, W. and Ames, J.B. (2009) 1H, 15N, and 13C Chemical Shift Assignments of the Mosquito Odorant-binding Protein-1 bound to MOP (Cqui-OBP1). Biomol. NMR Assignments, 3: 195-197.
Leal WS, Ishida Y, Pelletier J, Xu W, Rayo J, Xu X, Ames JB (2009) Olfactory proteins mediating chemical communication in the navel orangeworm moth, Amyelois transitella. PLoS One, 4:e7235.
Saludes, J., Ames, J.B. and Gervay-Hague J. (2009) Synthesis and Structural Characterization of Sialic Acid-Glutamic Acid Hybrid Foldamers as Conformational Surrogates of alpha-2,8-Linked Polysialic Acid. J. Am. Chem. Soc., 131: 5495-5505.
Lim, S., Peshenko, I., Dizhoor, A. and Ames J.B. (2009) The Effects of Ca2+, Mg2+ and Myristoylation on GCAP1 Structure and Stability. Biochemistry, 48:850-862.
Li, C., Chan, J., Haeseleer, F., Mikoshiba, K., Palczewski, K., Ikura, M. and Ames, J.B. (2009) Structural Insights into Ca2+-dependent Regulation of Inositol 1,4,5-trisphosphate Receptors by CaBP1. J. Biol. Chem., 284:2472-2481.
Wingard, J.N., Ladner, J., Vanarotti, M., Fisher, A., Robinson, H., Buchanan, K.T., Engman, D.M., and Ames, J.B. (2008) Structural Insights into Membrane-targeting by the Flagellar Calcium-binding Protein (FCaBP), a Myristoylated and Palmitoylated Calcium Sensor in T. cruzi. J. Biol. Chem., 283:23388-23396.
Xu, X., Li, Y., Rayo, J., Ishida, Y., Leal, W. and Ames, J.B. (2008) 1H, 15N, and 13C Chemical Shift Assignments of the Navel Orange Worm Pheromone-binding Protein-1 (Atra-PBP1). Biomol. NMR Assignments, 2:105-106.
Li, C. and Ames, J.B. (2008) NMR Assignments of Ca2+-bound CaBP1, a Calcium Sensor and Regulator of Neuronal Ca2+ Channels. Biomol. NMR Assignments, 2:61-63.
Lusin, J., Vanarotti, M., Li, C., Valiveti, A.and Ames, J.B. (2008) Structural Basis for Ca2+ Sensitive DNA Binding and Dimerization of DREAM, a Calcium Sensor for Pain Control. Biochemistry, 47:2252-2264.
Li, C. and Ames, J.B. (2007) NMR Assignments of Mg2+-bound CaBP1, a Calcium Sensor and Regulator of Neuronal Ca2+ Channels. J. Biomol. NMR, 1:77-79.