Membrane mimetic thermal proteome profiling (MM-TPP) towards mapping membrane protein-ligand dynamics

We combine the membrane mimetic (MM) Peptidisc with thermal proteome profiling (TPP) to screen membrane proteomes in detergent-free environments. Using whole mouse liver, we demonstrate the stabilization of integral membrane proteins (IMPs), specifically ATP-binding cassette transporters, through interactions with ATP and orthovanadate. Additionally, we assess the downstream effects of ATP hydrolysis products on IMP stability, such as that of GPCR purinergic receptors, and validate novel interactions with AlphaFold3