With the sequences of more and more complete genomes rapidly becoming available, the next step is to determine the structures and functions of the encoded proteins and how all these proteins come together to make a living cell. I am interested in the connection between a protein's sequence, structure and function(s). My lab uses biophysical, biochemical and bioinformatics methods in three research areas:

Transmembrane proteins
Our research on membrane proteins includes the mechanism of assembly of multidrug resistance transmembrane transporters, developing improved methods to express membrane proteins, and analyzing known structures to help understand the determinants of protein folding and structure determination in alpha-helical membrane proteins.

Moonlighting proteins
Many protein functions can be inferred from the known functions of homologous proteins, but determining protein functions is complicated by an increasing number of "moonlighting proteins", proteins that have more than one function where the multiple functions are not a result of splice variants, gene fusions, or multiple isoforms (Jeffery, C. J. Moonlighting Proteins. (1999) Trends in Biochemical Sciences. 24: 8-11). We are preparing a database of the known moonlighting proteins and performing an analysis of their sequences and structures. Knowing more about moonlighting proteins could help in predicting which additional proteins might also have a second function, which would be useful in determining the function(s) of the thousands of proteins identified through the genome projects and the functions of the "unknown" proteins whose structures were solved as part of the Protein Structure Initiative. In addition, since the ability of proteins to moonlight can complicate interpretation of the results of proteomics projects, identifying the roles of proteins in disease, and the selection of biomarkers, understanding which proteins moonlight can be important for both basic research and medicine.

Enzyme structures and mechanisms
Using a series of X-ray crystal structures, we identified the amino acids and conformational changes that are involved in the multistep catalytic mechanism of phosphoglucose isomerase, which is the second enzyme in glycolysis and also an extracellular cytokine and growth factor. We also have an ongoing collaboration to determine the structures and catalytic mechanisms of phosphomannose isomerases and other enzymes involved in biofilm formation.

Representative Publications

Jeffery, C. J. (2011) Neomorphic Moonlighting Functions in Disease. IUBMB Life (Special issue with the topic Moonlighting Proteins in Neurological Disorders). 63(7): 489-94.

Jeffery, C. J. (2011) Engineering Perplasmic Binding Proteins as Glucose Nanosensors. Nano Reviews 2: 5743-6.

Roux, C., F. Bhatt, J. Foret, B. de Courcy, N. Gresh, J.-P. Piquemal, C. J. Jeffery, and L. Salmon. (2011) Inhibition and Polarizable Molecular Mechanics Studies of Type I Phosphomannose Isomerases Reveal Information about the Reaction Mechanism. Proteins: Structure, Function, and Bioinformatics 79: 203-220.

Bhatt, F. and C. J. Jeffery. (2010) Expression, Detergent Solubilization, and Purification of a Membrane Transporter, the MexB Multidrug Resistance Protein. J Vis Exp. Dec 3;(46). pii: 2134. doi: 10.3791/2134.

Madhavan, V., F. Bhatt, and C. J. Jeffery. (2010) Recombinant Expression Screening of Pseudomonas aeruginosa Inner Membrane Proteins. BMC Biotechnology. 10: 83.

Arsenieva, D., B. L. Appavu, G. Mazock, and C. J. Jeffery. (2009) X-ray Crystal Structure of Trypanosoma brucei Phosphoglucose Isomerase Complexed with Glucose-6-phosphate at 1.6 Å Resolution. Proteins: Structure, Function, and Bioinformatics 74: 72-80

Jeffery, C. J. (2009) Moonlighting Proteins - An Update. Molecular Biosystems. 5: 345-50.