Researchers turn on switches that control protein-protein interactions

Postdocs Zhihong Guo and Demin Zhou and chemistry professor Peter G. Schultz of Scripps Research Institute have devised a technique in which small molecules are used as switches to turn protein-protein interactions on and off. The researchers introduced mutations into human growth hormone (hGH) and its cellular receptor that create a gap at the interface between the two proteins, decreasing by a million fold their usual affinity for each other. The idea is to have the ligand serve as an essential puzzle piece in the affinity relationship between two proteins. In another study, Tim Clackson, director of gene therapy at Ariad Pharmaceuticals, Cambridge, and colleagues have extended their ligand-reversible dimerization technique. In this technique called RAPID (regulated accumulation of proteins for immediate delivery) a ligand is used to induce secretion of a therapeutic protein by causing the breakup of an aggregate containing that protein.