The Indian Institute of Technology-Kanpur's Sciences and Bioengineering department has uncovered the molecular process of complement receptor activation and signalling, which is an important aspect of human immune response. The findings were reported in the international scientific journal Cell.
The scientists focused on the complement system and its reliance on chemicals known as anaphylatoxins, such as C3a and C5a, which interact with specific receptors known as C3aR and C5aR1. They attempted to understand how receptors work, including how they recognize their targets, activate, and govern signalling, which has largely remained a mystery.
In the study, the researchers used a powerful imaging technology known as cryo-EM to expose the inner workings of these receptors when activated by natural and synthesized chemicals. They observed distinct binding sites where anaphylatoxins connect to these receptors, providing insight into how the receptors get active and interact with signalling proteins, according to thestatesman.
The study also discovered a natural mechanism by which C5a's inflammatory response is lowered by removing a specific region of the molecule. It also discovered a peptide that selectively activates C3aR, proving that the receptors can react differently to different substances.
In essence, this study clarifies how anaphylatoxin receptors work, which are important pharmacological targets for inflammatory illnesses such as arthritis, asthma, sepsis, and many others. This research has significant implications for innovative drug discovery in a variety of human illness conditions.
Aside from Prof Arun K Shukla, the team included Manish K Yadav from the Department of BSBE IIT-K, Jagannath Maharana from the Department of BSBE IIT-K, Ramanuj Banerjee from the Department of BSBE IIT-K, Ravi Yadav from the Department of Biological Sciences at the University of Southern California, and Cornelius Gati from the Department of Biological Sciences at the University of Southern California.
