A paper published online in Nature Methods describes a general approach to genetically engineer proteins that are regulated by small chemical drugs.
Previous approaches that combined the strengths of genetics and pharmacology targeted specific proteins; the protein of choice was genetically modified in such a way that it became susceptible to small-molecule drugs. However, a general method for the engineering of drug-sensitive proteins has been lacking.
Mordechai Liscovitch and colleagues now introduce such a general method, which they call ligand interaction scan. They serially insert a short amino acid motif, specific for binding to a small-molecule ligand, into a protein of choice. Then, by scanning the activity of these mutant proteins, they are able to identify proteins that are activated or inhibited by the drug. Any protein can be made drug-sensitive by this approach; the only requirements for the scan are a read-out for protein activity and a cell-permeable drug, if the technique is to be carried out in live cells.
This method will aid in the functional analysis of proteins or even in the generation of transgenic organisms that carry proteins that are sensitive to a small-molecule drug.
Mordechai Liscovitch (Weizmann Institute of Science, Rehovot, Israel)
Abstract available online.
(C) Nature Methods press release.
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