A photoaffinity-probe based chemical proteomics strategy for mapping novel protein interactors of signaling lipids

Abstract

Small molecule metabolites play a key role in normal cellular functioning as cellular processes are most often regulated by their interactions with proteins. Enzyme-substrate, receptor-ligand, solute-carrier interactions etc. are examples of such metabolite-protein interactions. Therefore, deciphering the protein ligands of such metabolites helps us in understanding the downstream signalling in cells triggered by these metabolites and gain insights about the cellular functioning. One of the upcoming chemoproteomics technique called photoaffinity-based labelling (PAL) has been extremely beneficial in mapping the protein interactome of many ligands especially signalling lipids. In PAL, a ligand probe (which mimics a native ligand) is synthesised which carries two additional functional groups, a photocrosslinking group (which forms covalent bond with the proteins) and a bioorthogonal handle (to which a reporter tag can be ligated). The main aim of my doctoral research was to develop the PAL-based technology to