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Research Focus

Our research group is interested in understanding the intermolecular interactions of biological macromolecules: protein-protein, protein-nucleic acid, and protein-small molecule. Such interactions between proteins and ligands run nearly every aspect of biology, and we would like to understand them in quantitative, thermodynamic, and structural terms. To that end we study several examples using a range of experimental and theoretical biophysical tools. We apply ligand-binding theory, the quantitative treatment of interactions, to design experiments and analyse the results. Our experimental tools include calorimetry, surface plasmon resonance, NMR, x-ray crystallography, electronic spectroscopies, and others as each system requires. A recent addition to our toolkit is molecular dynamics simulations, which we apply to interpret experimental results and to design further experiments.

A fascinating non-linear property of protein interactions is cooperativity, also called allostery: the binding of one ligand alters the protein's affinity for another, as in the interaction of oxygen with hemoglobin that becomes progressively stronger as the binding sites fill. In cooperative systems changes in ligand concentration elicit distinct physiological responses. How proteins mediate cooperativity has been studied for over 50 years without clear answers. It is widely thought to represent a new strategy in targeted drug design, but we can't exploit it if we don't understand it. Our recent work on the arginine regulatory system of E. coli highlights how very large-scale dynamics of the protein contribute to cooperativity, and shows how they are profoundly altered by the ligand. It is now generally believed that all dynamic proteins are allosteric. However, we also study the tryptophan regulatory system of E. coli, which offers an apparent exception that can test our understanding.

Research Areas
Chemical Biology
Honors

Professor Carey has many long-standing collaborations in both the US and overseas. She holds a prestigious continuing appointment as a visiting scientist of the Czech Academy of Sciences. She was the 2005-2006 Tage Erlander guest professor of the Swedish National Science Foundation, the highest award given to visiting scholars. She considers this a particular honor because Tage Erlander was a noted educator and, as prime minister in the post-war years, is credited as the father of modern Swedish social democracy. In 2014 Professor Carey initiated and taught a new summer course in ligand-binding theory and practice sponsored by the Federation of European Biochemical Societies. In 2016, she was awarded an NSF INCLUDES Award for a pilot science educational program for the NJ state prisons. At home Professor Carey directs a long-running, NSF-funded training site (renewed through 2021) in biophysics research for undergraduates that brings students of the physical and mathematical sciences and engineering from schools with limited research opportunity to Princeton for a summer's research with our world-renowned faculty. REU students can spend a subsequent summer at the Czech Academy living and working in a renovated castle. Professor Carey is a member of numerous advisory and grant review committees, a frequent reviewer of manuscripts for a wide range of journals, and an editor of Biochimica et Biophysica Acta.

Selected Recent Publications

Sinha, D.; Shamayeva, K.; Ramasubramani, V.; Reha, D.; Bialevich, V.; Khabiri, M.; Guzanova, A.; Milbar, N.; Weiserova, M.; Csefalvay, E.; Carey, J.; Ettrich, R., "Interdomain communication in the endonuclease/motor subunit of type I restriction-modification enzyme EcoR124I." Journal of molecular modeling 2014, 20 (7), 2334-2334.

Pandey, S. K.; Reha, D.; Zayats, V.; Melichercik, M.; Carey, J.; Ettrich, R., "Binding-competent states for L-arginine in E. coli arginine repressor apoprotein." Journal of molecular modeling 2014, 20 (7), 2330-2330.

Kishko, I.; Carey, J.; Reha, D.; Brynda, J.; Winkler, R.; Harish, B.; Guerra, R.; Ettrichova, O.; Kukacka, Z.; Sheryemyetyeva, O.; Novak, P.; Kuty, M.; Smatanova, I. K.; Ettrich, R.; Lapkouski, M., "1.2 angstrom resolution crystal structure of Escherichia coli WrbA holoprotein." Acta Crystallographica Section D-Biological Crystallography 2013, 69, 1748-1757.

Slavov, N.; Carey, J.; Linse, S., "Calmodulin Transduces Ca2+ Oscillations into Differential Regulation of Its Target Proteins." Acs Chemical Neuroscience 2013, 4 (4), 601-612.

Carey, J.; Benoff, B.; Harish, B.; Yuan, L.; Lawson, C. L., "Environment-dependent long-range structural distortion in a temperature-sensitive point mutant." Protein Science 2012, 21 (1), 63-74.

Kopecky, V.; Kohoutova, J.; Lapkouski, M.; Hofbauerova, K.; Sovova, Z.; Ettrichova, O.; Gonzalez-Perez, S.; Dulebo, A.; Kaftan, D.; Smatanova, I. K.; Revuelta, J. L.; Arellano, J. B.; Carey, J.; Ettrich, R., "Raman Spectroscopy Adds Complementary Detail to the High-Resolution X-Ray Crystal Structure of Photosynthetic PsbP from Spinacia oleracea." Plos One 2012, 7 (10).

Wolfova, J.; Smatanova, I. K.; Brynda, J.; Mesters, J. R.; Lapkouski, M.; Kuty, M.; Natalello, A.; Chatterjee, N.; Chern, S.-Y.; Ebbel, E.; Ricci, A.; Grandori, R.; Ettrich, R.; Carey, J., "Structural organization of WrbA in apo- and holoprotein crystals." Biochimica Et Biophysica Acta-Proteins and Proteomics 2009, 1794 (9), 1288-1298.

Xue, W.-F.; Szuepankiewicz, O.; Thulin, E.; Linse, S.; Carey, J., "Role of protein surface charge in monellin sweetness." Biochimica Et Biophysica Acta-Proteins and Proteomics 2009, 1794 (3), 410-420

Strawn, R.; Melichereik, M.; Green, M.; Stockner, T.; Carey, J.; Ettrich, R., "Allosteric Mechanism of Hexameric E. coli Arginine Repressor." Journal of Biomolecular Structure & Dynamics 2009, 26 (6), 849-+.

Lapkouski, M.; Panjikar, S.; Janscak, P.; Smatanova, I. K.; Carey, J.; Ettrich, R.; Csefalvay, E., "Structure of the motor subunit of type I restriction-modification complex EcoR124I." Nature Structural & Molecular Biology 2009, 16 (1), 94-95.

Wolfova, J.; Mesters, J. R.; Brynda, J.; Grandori, R.; Natalello, A.; Carey, J.; Smatanova, I. K., "Crystallization and preliminary diffraction analysis of Escherichia coli WrbA in complex with its cofactor flavin mononucleotide." Acta Crystallographica Section F-Structural Biology and Crystallization Communications 2007, 63, 571-575.

Natalello, A.; Doglia, S. M.; Carey, J.; Grandori, R., "Role of flavin mononucleotide in the thermostability and oligomerization of Escherichia coli stress-defense protein WrbA." Biochemistry 2007, 46 (2), 543-553.

Brauner, A.; Carey, J.; Henriksson, M.; Sunnerhagen, M.; Ehrenborg, E., "Open-ended assignments and student responsibility." Biochemistry and Molecular Biology Education 2007, 35 (3), 187-192.

Carey, J.; Lindman, S.; Bauer, M.; Linse, S., "Protein reconstitution and three-dimensional domain swapping: Benefits and constraints of covalency." Protein Science 2007, 16 (11), 2317-2333.

Carey, J.; Brynda, J.; Wolfova, J.; Grandori, R.; Gustavsson, T.; Ettrich, R.; Smatanova, I. K., "WrbA bridges bacterial flavodoxins and eukaryotic NAD(P)H: quinone oxidoreductases." Protein Science 2007, 16 (10), 2301-2305.

Ji, H.-F.; Shen, L.; Carey, J.; Grandori, R.; Zhang, H.-Y., "Why WrbA is weaker than flavodoxin in binding FMN. A molecular modeling study." Journal of Molecular Structure-Theochem 2006, 764 (1-3), 155-160.

Noll, G.; Kozma, E.; Grandori, R.; Carey, J.; Schodl, T.; Hauska, G.; Daub, J., "Spectroelectrochemical investigation of a flavoprotein with a flavin-modified gold electrode." Langmuir 2006, 22 (5), 2378-2383.

Jin, L. H.; Xue, W. F.; Fukayama, J. W.; Yetter, J.; Pickering, M.; Carey, J., "Asymmetric allosteric activation of the symmetric ArgR hexamer." Journal of Molecular Biology 2005, 346 (1), 43-56.

Wolfova, J.; Grandori, R.; Kozma, E.; Chatterjee, N.; Carey, J.; Smatanova, I. K., "Crystallization of the flavoprotein WrbA optimized by using additives and gels." Journal of Crystal Growth 2005, 284 (3-4), 502-505.

Samalikova, M.; Carey, J.; Grandori, R., "Assembly of the hexameric Escherichia coli arginine repressor investigated by nano-electrospray ionization time-of-flight mass spectrometry." Rapid Communications in Mass Spectrometry 2005, 19 (18), 2549-2552.

Pursglove, S. E.; Fladvad, M.; Bellanda, M.; Moshref, A.; Henriksson, M.; Carey, J.; Sunnerhagen, M., "Biophysical properties of regions flanking the bHLH-Zip motif in the p22 Max protein." Biochemical and Biophysical Research Communications 2004, 323 (3), 750-759.

 

Xue, W. F.; Carey, J.; Linse, S., "Multi-method global analysis of thermodynamics and kinetics in reconstitution of monellin." Proteins-Structure Function and Bioinformatics 2004, 57 (3), 586-595.

Lawson, C. L.; Benoff, B.; Berger, T.; Berman, H. M.; Carey, J., "E-coli trp forms a domain-swapped array in aqueous alcohol." Structure 2004, 12 (6), 1099-1108.

Tyler, R.; Pelczer, I.; Carey, J.; Copie, V., "Three-dimensional solution NMR structure of Apo-L75F-TrpR, a temperature-sensitive mutant of the tryptophan repressor protein." Biochemistry 2002, 41 (40), 11954-11962.

Szwajkajzer, D.; Dai, L. H.; Fukayama, J. W.; Abramczyk, B.; Fairman, R.; Carey, J., "Quantitative analysis of DNA binding by the Escherichia coli arginine repressor." Journal of Molecular Biology 2001, 312 (5), 949-962.