The Multiple Lives of Moonlighting Proteins
Moonlighting proteins comprise a class of multifunctional proteins in which a single polypeptide chain has multiple biochemical functions that are not due to gene fusion events. Examples include cytosolic enzymes that are also transcription factors, crystallins, chaperones, extracellular growth factors, or cell surface adhesins. The variety of known moonlighting proteins, the multiple ways in which one protein can have multiple functions, the potential benefits to the organism of combining two functions in one protein, and the methods proposed for a protein to evolve a second function suggest that moonlighting proteins might be common.
The ability of a protein to moonlight in different multi-protein complexes or pathways can complicate the prediction of protein function from sequence or structure and the annotation of sequence databases. To date, most moonlighting functions have been found by serendipity. There is currently no straightforward method to identify which proteins moonlight, or for determining if a protein of interest is a moonlighting protein. In addition, sequence homologues of moonlighting proteins often do not perform both functions. We are using biochemical methods and X-ray crystallography to study individual moonlighting proteins. We are also organizing information about the sequences, structures, functions and functional sites of the over 200 known moonlighting proteins into the web-based MoonProt database.
Short Bio: Constance (Connie) Jeffery obtained a B.S. in biology at the Massachusetts Institute of Technology (MIT) and a Ph.D. in biochemistry at the University of California at Berkeley. She is currently an associate professor of biological sciences and an adjunct professor of bioengineering at the University of Illinois at Chicago. The Jeffery lab uses biophysical and biochemical methods along with computer-based structure analysis to study the connections between protein sequences, structures, and functions. By solving six X-ray crystal structures of the moonlighting protein phosphoglucose isomerase/autocrine motility factor (PGI/AMF) with different ligands bound, lab members developed a model of the multistep catalytic mechanism for this multifunctional enzyme/growth factor. The lab is also involved in the development of improved technologies for membrane protein expression and for identifying ligands for proteins. Prof. Jeffery developed the idea/concept of moonlighting proteins, and wrote several articles describing examples of moonlighting proteins from the literature, their methods to switch between functions, possible methods of evolution, and potential benefits to cells.