Velcro-Like Protein Both Activates And Tracks Biochemical Targets

With an engineered protein, researchers have developed an integrated way to control enzyme activity and track it via fluorescence (Science, DOI: 10.1126/science.1226854). Manipulating proteins with light is nothing new—scientists have used both small molecules and other proteins to take control. The existing approaches, however, are difficult to generalize to diverse proteins. Xin X. Zhou, Michael Z. Lin, and coworkers at Stanford University have now adapted Dronpa, a fluorescent protein from coral, to the task. Left alone, their glowing Dronpa variants stick to one another like Velcro. Under blue-green light (about 500 nm), the dimers or tetramers fall apart, dimming in fluorescence. Lin’s team tacked a Dronpa unit to each end of the proteins they wished to study, including a hepatitis C protease and a protein linked to cell locomotion. The Dronpas stuck together, caging the proteins and inactivating them. Blue-green light released the cage, restoring protein activity. The researchers tracked activation through the proteins’ fading fluorescence. Lin’s lab is refining the technology so that it will work with any part of a protein, not just the ends. Stanford has filed a patent application on the technique.