Deconvoluting the biology and druggability of protein lipidation using chemical proteomics. (February 2021)

• Record Type: Journal Article
• Authors: Losada de la Lastra, Ana; Hassan, Sarah; Tate, Edward W.
• Is Part Of: Current opinion in chemical biology. Volume 60(2021)
• Page Start: 97
• Page End: 112
• Publication Date: 2021-02
• Subjects: Protein lipidation -- N-Myristoylation -- S-Prenylation -- S-Acylation -- Chemical proteomics -- Biorthogonal labeling -- Click chemistry -- Drug discovery -- Viral proteome -- Bacterial effectors -- Parasite proteome; ABHD α/β hydrolase fold domain -- ABE acyl-biotin exchange -- AzMyr azido myristic acid -- Cys cysteine -- DTPD 2, 2′-dithiodipyridine -- EDTA ethylenediaminetetraacetic acid -- FSP ferroptosis suppressor protein 1 -- FT farnesyltransferase -- FTI farnesyltransferase inhibitor -- Gly glycine -- GNAT GCN5-related N-acetyltransferase -- HA hydroxylamine -- HDACs histone deacetylases -- HMG-CoA 3-hydroxy-3-methylglutaryl-coenzyme a -- IFITM3 Interferon-induced transmembrane protein 3 -- IFN interferon -- MetAP methionine aminopeptidase -- NAT N-acetyl transferase -- NCX1 sodium-calcium exchanger -- NMT N-myristoyltransferase -- PEG polyethylene glycol -- PTI prenyltransferase inhibitor -- PTM post-translational modification -- RAC resin-assisted Capture -- REP Rab escort protein -- SIRT sirtuins -- SNARE soluble N-ethylmaleimide–sensitive factor-attachment protein receptor -- SrtA sortase A -- STING stimulator of interferon genes -- SILAC stable isotope labeling -- MYR N-myristoylation -- YKT6 SNARE protein Ykt6 -- YnMyr alkyne myristic acid -- YnF alkyne farnesol -- YnGG alkyne geranylgeraniol; Bioorganic chemistry -- Periodicals; Biology -- Periodicals; Biochemistry -- Periodicals; Clinical biochemistry -- Periodicals; Biochemistry -- Periodicals; Chimie bio-organique -- Périodiques; Biologie -- Périodiques; 572.05
• DOI: 10.1016/j.cbpa.2020.10.002
• Languages: English
• ISSNs: 1367-5931

Abstract

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. Graphical abstract: Image 1