Chemical Methods for Monitoring Protein Fatty Acylation

Abstract

Protein fatty acylation encompasses different forms of lipidation and plays critical roles in regulating protein membrane binding and trafficking, stability, and activity. Due to the importance of protein fatty acylation in many different biological processes, there has been significant interest in sensitive detection and enrichment methods. To facilitate the analysis of protein fatty acylation in biology, fatty acid analogs bearing alkyne or azide tags have been developed that enable fluorescent imaging and proteomic profiling of modified proteins using bioorthogonal chemistry methods. In this chapter, we will briefly introduce various kinds of protein fatty acylation, their regulation and function, as well as associations with human diseases. The focus of the chapter will be on metabolic labeling using chemical reporters of protein fatty acylation and other complementary approaches to analyze protein S-fatty acylation, including ABE, acyl-RAC, and acyl-PEG exchange methods.