Investigating the Regulation of PI3Kγ




Evans, John T.

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Phosphoinositide 3-kinase gamma (PI3Kγ) is a key signalling protein in the immune system. It helps to control immune cell movement among other functions, and it is a potential drug target for a variety of immune disorders. Importantly, there are two forms of PI3Kγ in cells. These two forms play different roles, and are activated differently by receptors on the surface of the cell. We aimed to understand the structural basis for this difference in activation. Based on previous work and an artificial intelligence model, we identified a putative binding interface. We designed a mutant protein where we changed that interface and measured the result with a biochemical assay. We demonstrated that the interface is indeed responsible for the different activation of the two forms of PI3Kγ. This understanding of PI3Kγ activation could be used in future drug development for immune disorders.



cell biology, p84, p101, p110, GPCR, PI3K