IIT Kanpur researchers visualize communication of G-protein coupled receptors, paves way for new drug discovery

Delhi, 24 May 2023: A gaggle of researchers led by Prof. Arun Okay Shukla within the Department of Biological Sciences and Bioengineering on the Indian Institute of Technology Kanpur (IIT-Okay) has unraveled a beforehand unknown mechanism that regulates an vital class of drug targets often called G protein-coupled receptors. The discovery has vital implications for not solely understanding the elemental mechanism of mobile signaling in our physique but in addition has the potential to facilitate novel drug discovery for a number of human illness circumstances. The research printed within the May difficulty of the worldwide journal, Molecular Cell has been carried out utilizing a cutting-edge know-how often called cryogenic-electron microscopy (cryo-EM).

The cells in our physique are surrounded by a membrane that harbors a particular kind of protein molecule often called receptors. These receptors are vital for our physique to sense totally different chemical compounds and hormones, and reply accordingly by activating particular physiological responses. One specific class of receptors often called G protein-coupled receptors (GPCRs), is concerned in regulating coronary heart perform, blood stress, psychological issues, and our conduct. Several medicine similar to these used for melancholy, coronary heart failure, most cancers, and hypertension work by modulating these receptor proteins.

The perform of GPCRs is regulated by one other household of proteins in our physique often called arrestins, which bind to GPCRs and management their perform and physiological responses. However, an entire understanding of GPCR-arrestin interplay has been largely elusive thus far. The researchers have now visualized the cross-talk of GPCRs and arrestins in nice element utilizing cutting-edge know-how, cryogenic-electron microscopy (cryo-EM). The identical has allowed the workforce to find a novel mechanism that’s accountable for regulating the perform of GPCRs in our our bodies.

Says Prof Shukla, “This research has opened up novel instructions for bettering the presently present medicines by decreasing their side-effects, and in addition supplies a possibility for discovering new drugs for a number of human illness circumstances. For instance, the chemokine receptor that’s one of the receptors investigated on this research has vital roles in breast most cancers development whereas the complement receptors additionally investigated listed below are vital targets for treating inflammatory issues similar to rheumatoid arthritis.”

The researchers at the moment are working within the course of novel drug discovery in collaboration with a number of worldwide laboratories together with research in animal fashions.

This research is led by Prof. Arun Okay. Shukla and is co-authored by Ph.D. college students Mr. Jagannath Maharana, Ms. Parishmita Sarma, and Ms. Shirsha Saha, post-doctoral fellows Dr. Ramanuj Banerjee and Dr. Manish Yadav, and undertaking fellows Mr. Sayantan Saha and Mr. Vinay Singh. The research additionally consists of Dr. Mohamed Chami from the University of Basel in Switzerland as a collaborator. This research is supported by the DBT Wellcome Trust India Alliance and Science and Engineering Research Board (SERB).

Dr. Shukla can be spearheading the institution of a National cryo-EM facility at IIT Kanpur that’s supported by SERB, and anticipated to be practical later this 12 months.

Journal reference:

Shukla AK, Maharana J, Sarma P, Yadav MK, Saha S, Singh V, Saha S, Chami M, Banerjee R. “ Structural snapshots uncover a key phosphorylation motif in GPCRs driving β-arrestin activation”. 2023. Molecular Cell. May: https://doi.org/10.1016/j.molcel.2023.04.025