Global profiling of protein lipidation using chemical proteomic technologies.
Bottom Line: Protein lipidation is unique amongst post-translational modifications (PTMs) in enabling direct interaction with cell membranes, and is found in every form of life.Global whole-proteome profiling of protein lipidation lies beyond the range of standard methods, but is well-suited to metabolic tagging with small 'clickable' chemical reporters that do not disrupt metabolism and function; chemoselective reactions are then used to add multifunctional labels exclusively to tagged-lipidated proteins.This chemical proteomic technology has opened up the first quantitative whole-proteome studies of the known major classes of protein lipidation, and the first insights into their full scope in vivo.
Affiliation: Department of Chemistry, Imperial College London, Exhibition Road, London SW7 2AZ, UK. Electronic address: email@example.com.Show MeSH
Mentions: The context of human infection recently provided the first example of reversal of N-terminal N-myristoylation; in this study, enzymatic treatment of YnMyr-tagged cell lysates revealed that the N-myristoylglycine moiety can be hydrolyzed by a secreted bacterial effector protein with cysteine protease activity, the Shigella virulence factor IpaJ [14•]. This process is itself irreversible since the N-terminal glycine is also cleaved from the protein, and allows Shigella to exploit host trafficking pathways during bacterial infection. In the future, IpaJ may also prove a useful and complementary tool for analysis of N-acylation, although its substrate scope has yet to be determined in cells (Figure 2).
Affiliation: Department of Chemistry, Imperial College London, Exhibition Road, London SW7 2AZ, UK. Electronic address: firstname.lastname@example.org.