Deconvoluting the biology and druggability of protein lipidation using chemical proteomics |
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Affiliation: | 1. Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), 91198, Gif-sur-Yvette, France |
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Abstract: | Lipids are indispensable cellular building blocks, and their post-translational attachment to proteins makes them important regulators of many biological processes. Dysfunction of protein lipidation is also implicated in many pathological states, yet its systematic analysis presents significant challenges. Thanks to innovations in chemical proteomics, lipidation can now be readily studied by metabolic tagging using functionalized lipid analogs, enabling global profiling of lipidated substrates using mass spectrometry. This has spearheaded the first deconvolution of their full scope in a range of contexts, from cells to pathogens and multicellular organisms. Protein N-myristoylation, S-acylation, and S-prenylation are the most well-studied lipid post-translational modifications because of their extensive contribution to the regulation of diverse cellular processes. In this review, we focus on recent advances in the study of these post-translational modifications, with an emphasis on how novel mass spectrometry methods have elucidated their roles in fundamental biological processes. |
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Keywords: | Protein lipidation Chemical proteomics Biorthogonal labeling Click chemistry Drug discovery Viral proteome Bacterial effectors Parasite proteome ABHD" },{" #name" :" keyword" ," $" :{" id" :" kwrd0070" }," $$" :[{" #name" :" text" ," _" :" α/β hydrolase fold domain ABE" },{" #name" :" keyword" ," $" :{" id" :" kwrd0080" }," $$" :[{" #name" :" text" ," _" :" acyl-biotin exchange AzMyr" },{" #name" :" keyword" ," $" :{" id" :" kwrd0090" }," $$" :[{" #name" :" text" ," _" :" azido myristic acid Cys" },{" #name" :" keyword" ," $" :{" id" :" kwrd0100" }," $$" :[{" #name" :" text" ," _" :" cysteine DTPD" },{" #name" :" keyword" ," $" :{" id" :" kwrd0110" }," $$" :[{" #name" :" text" ," _" :" 2,2′-dithiodipyridine EDTA" },{" #name" :" keyword" ," $" :{" id" :" kwrd0120" }," $$" :[{" #name" :" text" ," _" :" ethylenediaminetetraacetic acid FSP" },{" #name" :" keyword" ," $" :{" id" :" kwrd0130" }," $$" :[{" #name" :" text" ," _" :" ferroptosis suppressor protein 1 FT" },{" #name" :" keyword" ," $" :{" id" :" kwrd0140" }," $$" :[{" #name" :" text" ," _" :" farnesyltransferase FTI" },{" #name" :" keyword" ," $" :{" id" :" kwrd0150" }," $$" :[{" #name" :" text" ," _" :" farnesyltransferase inhibitor Gly" },{" #name" :" keyword" ," $" :{" id" :" kwrd0160" }," $$" :[{" #name" :" text" ," _" :" glycine GNAT" },{" #name" :" keyword" ," $" :{" id" :" kwrd0170" }," $$" :[{" #name" :" text" ," _" :" GCN5-related N-acetyltransferase HA" },{" #name" :" keyword" ," $" :{" id" :" kwrd0180" }," $$" :[{" #name" :" text" ," _" :" hydroxylamine HDACs" },{" #name" :" keyword" ," $" :{" id" :" kwrd0190" }," $$" :[{" #name" :" text" ," _" :" histone deacetylases HMG-CoA" },{" #name" :" keyword" ," $" :{" id" :" kwrd0200" }," $$" :[{" #name" :" text" ," _" :" 3-hydroxy-3-methylglutaryl-coenzyme a IFITM3" },{" #name" :" keyword" ," $" :{" id" :" kwrd0210" }," $$" :[{" #name" :" text" ," _" :" Interferon-induced transmembrane protein 3 IFN" },{" #name" :" keyword" ," $" :{" id" :" kwrd0220" }," $$" :[{" #name" :" text" ," _" :" interferon MetAP" },{" #name" :" keyword" ," $" :{" id" :" kwrd0230" }," $$" :[{" #name" :" text" ," _" :" methionine aminopeptidase NAT" },{" #name" :" keyword" ," $" :{" id" :" kwrd0240" }," $$" :[{" #name" :" text" ," $$" :[{" #name" :" italic" ," _" :" N" },{" #name" :" __text__" ," _" :" -acetyl transferase NCX1" },{" #name" :" keyword" ," $" :{" id" :" kwrd0250" }," $$" :[{" #name" :" text" ," _" :" sodium-calcium exchanger NMT" },{" #name" :" keyword" ," $" :{" id" :" kwrd0260" }," $$" :[{" #name" :" text" ," $$" :[{" #name" :" italic" ," _" :" N" },{" #name" :" __text__" ," _" :" -myristoyltransferase PEG" },{" #name" :" keyword" ," $" :{" id" :" kwrd0270" }," $$" :[{" #name" :" text" ," _" :" polyethylene glycol PTI" },{" #name" :" keyword" ," $" :{" id" :" kwrd0280" }," $$" :[{" #name" :" text" ," _" :" prenyltransferase inhibitor PTM" },{" #name" :" keyword" ," $" :{" id" :" kwrd0290" }," $$" :[{" #name" :" text" ," _" :" post-translational modification RAC" },{" #name" :" keyword" ," $" :{" id" :" kwrd0300" }," $$" :[{" #name" :" text" ," _" :" resin-assisted Capture REP" },{" #name" :" keyword" ," $" :{" id" :" kwrd0310" }," $$" :[{" #name" :" text" ," _" :" Rab escort protein SIRT" },{" #name" :" keyword" ," $" :{" id" :" kwrd0320" }," $$" :[{" #name" :" text" ," _" :" sirtuins SNARE" },{" #name" :" keyword" ," $" :{" id" :" kwrd0330" }," $$" :[{" #name" :" text" ," _" :" soluble N-ethylmaleimide–sensitive factor-attachment protein receptor SrtA" },{" #name" :" keyword" ," $" :{" id" :" kwrd0340" }," $$" :[{" #name" :" text" ," _" :" sortase A STING" },{" #name" :" keyword" ," $" :{" id" :" kwrd0350" }," $$" :[{" #name" :" text" ," _" :" stimulator of interferon genes SILAC" },{" #name" :" keyword" ," $" :{" id" :" kwrd0360" }," $$" :[{" #name" :" text" ," _" :" stable isotope labeling MYR" },{" #name" :" keyword" ," $" :{" id" :" kwrd0370" }," $$" :[{" #name" :" text" ," $$" :[{" #name" :" italic" ," _" :" N" },{" #name" :" __text__" ," _" :" -myristoylation YKT6" },{" #name" :" keyword" ," $" :{" id" :" kwrd0380" }," $$" :[{" #name" :" text" ," _" :" SNARE protein Ykt6 YnMyr" },{" #name" :" keyword" ," $" :{" id" :" kwrd0390" }," $$" :[{" #name" :" text" ," _" :" alkyne myristic acid YnF" },{" #name" :" keyword" ," $" :{" id" :" kwrd0400" }," $$" :[{" #name" :" text" ," _" :" alkyne farnesol YnGG" },{" #name" :" keyword" ," $" :{" id" :" kwrd0410" }," $$" :[{" #name" :" text" ," _" :" alkyne geranylgeraniol |
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