1-Jan-2017: Drug discovery for GPCR signalling made easy by IIT Kanpur

Researchers have shown that the regulation of G Protein-Coupled Receptors (GPCRs) by new drugs can be simpler than generally thought. It can be mediated by engaging only the end of the receptor, which is called the tail of the receptor.

With this discovery, finding new drugs that bind to G Protein-Coupled Receptors (GPCRs) which are central to almost every physiological process in our body such as vision, taste, immune response and cardiovascular regulation becomes easier.

Nearly 50% of prescription drugs currently available in the market for the treatment of blood pressure, heart failure, diabetes, obesity, cancer and many other human diseases target GPCR receptors. All these drugs bind to their respective receptors and either activate or stop their signalling.

General understanding is that effector proteins have to simultaneously bind at two sites — the tail of the receptor and the core of the receptor — for the drug to become effective in pulling the receptor inside the cell. Through specific engineering of the receptor researchers basically disrupted one of the two binding sites, namely the core of receptor. They found that even without the second site, the protein was able to pull the receptor inside the cell by binding just to the tail of the receptor. There is a key region in the core which the researchers genetically deleted thereby making the core of the receptor ineffective.