Key discovery
A molecular mechanism of complement receptor activation and signalling, which is a vital part of our immune response have been discovered by a team of scientists led by Prof Arun Shukla at IIT Kanpur today.
The team carried out their research based on the complement system and its dependence on molecules called anaphylatoxins, like C3a and C5a, which interact with specific receptors known as C3aR and C5aR1. How the receptors work and recognize their targets, activate, and control signalling were tried to be understand which remained a mystery so far.
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The scientists used a powerful imaging technique called cryo-EM in the study to reveal the inner workings of these receptors when they are activated by natural and synthetic compounds. They have discovered unique binding pockets where anaphylatoxins attach to these receptors, shedding light on how the receptors become activated and engage with signalling proteins.
Apart from this, the study also uncovered a natural mechanism where C5a’s inflammatory response is reduced through the removal of a specific part of the molecule. It also identified a peptide that selectively activates C3aR, demonstrating that the receptors can respond differently to various compounds.
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This research also provides a clearer understanding of how anaphylatoxin receptors function, which are important drug targets for inflammatory disorders like arthritis, asthma, sepsis, and many other disorders. A great chance has evolved for the discovery of medicines for several diseases.
