Protein Regulation, By Design

By connecting two proteins at "hot spots" on their surfaces, researchers have designed a hybrid protein in which the activity of one protein is controlled by that of the other (Science 2008, 322, 438). This type of construct may prove to be a general strategy to engineer regulation into proteins, which could be useful for controlling enzymes in industrial bioreactor settings. Rama Ranganathan of the University of Texas Southwestern Medical Center, Stephen J. Benkovic of Pennsylvania State University, and coworkers borrowed a light-sensing protein module from the oat plant to influence the activity of a dihydrofolate reductase enzyme from Escherichia coli. They used statistical coupling analysis, a computational method pioneered by Ranganathan, to find physically connected networks of amino acid residues that link each protein's active site to surface-exposed residues. They next made several hybrid proteins, each linked at different locations. Shining white light on the hybrids doubled the enzyme's activity, but only when the proteins were connected via specific surface hot spots. The team now plans to determine how the signal travels from the light-sensing module to the enzyme.