Understanding the interaction and binding affinity of IL-2 with the receptors IL-2Rα, IL-2Rβ and IL-2Rγc controls the...

Cytokines Interleukin-2 (IL-2) and its IL-2R receptors play an important role in regulating the immune system and cellular functions. The high binding affinity of IL-2 with its trimeric receptor proteins IL-2Rα, IL-2Rβ, and IL-2Rγc directly controls the signal transduction thereby triggering critical biological responses like T cell activation and proliferation. And these are the key proteins being used for cancer immunotherapy as they activate and proliferates immune cells. Binding of IL-2 with IL-2R receptor proteins enhances the anti-tumour immune responses. Strong interaction of residues at the interface of IL-2 and each IL-2R receptor is essential for good binding affinity. For sustained signal transduction, high binding affinity is always expected, even during the dynamic state of the complex also. Hence, it is essential to know the interactions and binding affinity at the dynamic state, which is possible from the molecular dynamics (MD) simulation was carried out at 500ns for the IL-2 and its receptors IL-2Rαβγc. The interactions at the interface of IL-2/IL-2Rα, IL-2/IL-2Rβ and IL-2/IL-2Rγc receptor complexes and their binding affinity have been studied at different time scales. The results of this computational study reveals that at the dynamic state, the IL-2Rα receptor has high interface area exhibit high binding affinity than IL-2Rβ and IL-2Rγc receptors. Further this study confirms that, the combined interactions of this quaternary complex IL-2/IL-2αβγc restores the high binding affinity as found in apo protein complex; hence, presumably the signal transduction continues to happen even at the high dynamic state of the complex also.