The human genome project yielded the sequences of over 20,000 proteins. Elucidating the roles these proteins play in health and disease, and also how they can be used and/or modified for the development of novel therapeutics, biomaterials, biosensors, methods for energy production and methods for environmental remediation, will be aided by a better understanding of how a protein's amino acid sequence determines its structure and how structure determines function.  Members of the Jeffery lab are using biophysical and biochemical methods along with computer-based structure analysis in several projects to study the connections between protein sequences, structures, and functions.  Current research topics include moonlighting proteins, pseudoenzymes, and proteins involved in cancer and IBD.

Protein Sequences, Structures, and Functions

     Members of the Jeffery Lab use biochemistry, biophysics (X-ray crystallography), and bioinformatics to understand how protein sequences and structures relate to their functions.  Current research topics include moonlighting proteins, pseudoenzymes, metamorphic proteins and proteins involved in cancer and IBD.  Studies of individual proteins involve combinations of X-ray crystallography, ligand binding assays, catalytic activity assays, mutagenesis, and/or computer-based ligand docking simulations or analysis of disease-causing genetic mutations.  Additional computer-based projects in the analysis of protein sequence, structure and function are being performed to develop better methods to predict a protein's function(s) from its sequence or structure.
       One of our long-term projects involves moonlighting proteins.  Hundreds of proteins have been found to be moonlighting proteins, where a single protein performs multiple physiologically relevant biochemical or biophysical functions performed by a single polypeptide. (Jeffery, C. J. Moonlighting Proteins. (1999) Trends in Biochemical Sciences. 24: 8-11). We created a database of the known moonlighting proteins (The MoonProt Database at moonlightingproteins.org) and are performing an analysis of their sequences and structures. Knowing more about moonlighting proteins could help in predicting which additional proteins might also have multiple functions, which would be useful in determining the function(s) of the thousands of proteins identified through the genome projects, interpreting data from proteomics projects and annotating protein sequence and structural databases. In addition, information about the structures and functions of moonlighting proteins can be helpful in understanding how novel protein functional sites evolved on an ancient protein scaffold, which can help in the design of proteins with novel functions.

Nicole presenting her poster
​at the 2022 MWFold meeting.

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