A group of researchers led by Prof Arun K Shukla in the Department of Biological Sciences and Bioengineering at the Indian Institute of Technology, Kanpur, have unravelled a previously unknown mechanism that regulates an important class of drug targets known as G protein-coupled receptors.

The discovery has important implications for not only understanding the fundamental mechanism of cellular signalling in our body but also facilitating novel drug discovery.

Cell membranes in our body harbour a special type of protein molecules known as receptors.

These receptors sense different chemicals and hormones and respond accordingly by activating specific physiological responses.

The G protein-coupled receptors (GPCRs) are involved in regulating heart function, blood pressure, mental disorders, and our general behaviour.

Several drugs, such as those used for depression, heart failure, cancer, and hypertension, work by modulating these receptor proteins.

The function of the GPCRs is regulated by another family of proteins known as arrestins, which bind to GPCRs and control their function and physiological responses.

However, a complete understanding of GPCR-arrestin interaction has been mostly elusive so far.

“The researchers have now visualised the cross-talk of GPCRs and arrestins in great detail using the cutting-edge technology cryogenic-electron microscopy (cryo-EM). The same has allowed the team to discover a novel mechanism that is responsible for regulating the function of GPCRs in our body,” says a press release from IIT-Kanpur.

“This study has opened up novel directions for improving the currently existing medicines by lowering their side-effects, and also provides an opportunity for discovering new medicines for several human disease conditions,” says Prof Shukla.

“For example, the chemokine receptor, which is one of the receptors investigated in this study, has important role in breast cancer progression.”