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Weizmann Researchers Developed Control Switch for Protein Activity

Our bodies could not maintain their existence without thousands of proteins performing myriad vital tasks within cells. Since malfunctioning proteins can cause disease , the study of protein structure and function can lead to the development of drugs and treatments for numerous disorders. Despite enormous research efforts led by scientists worldwide, the cellular function of numerous proteins is still unknown.

To reveal this function, scientists perform various genetic manipulations to increase or, conversely, decrease the production of a certain protein, but existing manipulations of this sort are complicated and do not fully meet the researchers needs.

Prof. Mordechai Moti Liscovitch and graduate student Oran Erster of the Weizmann Institutes Biological Regulation Department, together with Dr. Miri Eisenstein of Chemical Research Support, have recently developed a unique switch that can control the activity of any protein, raising it several-fold or stopping it almost completely. The method provides researchers with a simple and effective tool for exploring the function of unknown proteins, and in the future the new technique may find many additional uses.

The switch has a genetic component and a chemical component: Using genetic engineering, the scientists insert a short segment of amino acids into the amino acid sequence making up the protein. This segment is capable of binding strongly and selectively to a particular chemical drug, which affects the activity level of the engineered protein by increasing or reducing it. When the drug is no longer applied, or when it is removed from the system, the protein returns to its natural activity level.

As reported recently in the journal Nature Methods, the first stage of the method consists of preparing a set of genetically engineered proteins (called a library in scientific language) with the amino acid segment inserted in different places. In the second stage, the engi
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