Deconvoluting the biology and druggability of protein lipidation using chemical proteomics

Lipids are indispensable cellular building blocks, and their post-translational attachment to proteins makes them important regulators of many biological processes. Dysfunction protein lipidation is also implicated in pathological states, yet its systematic analysis presents significant challenges. Thanks innovations chemical proteomics, can now be readily studied by metabolic tagging using functionalized lipid analogs, enabling global profiling lipidated substrates mass spectrometry. This has spearheaded the first deconvolution full scope a range contexts, from cells pathogens multicellular organisms. Protein N-myristoylation, S-acylation, S-prenylation most well-studied modifications because extensive contribution regulation diverse In this review, we focus on recent advances study these modifications, with an emphasis how novel spectrometry methods have elucidated roles fundamental