Mapping the myristoylome through a complete understanding of protein myristoylation biochemistry. (January 2022)

• Record Type: Journal Article
• Authors: Giglione, Carmela; Meinnel, Thierry
• Is Part Of: Progress in lipid research. Volume 85(2022)
• Publication Date: 2022-01
• Subjects: N-terminus -- Cysteine -- Glycine -- Lysine -- Compartments -- Acylation; AcCoA acetyl-coenzyme A -- ACP acyl carrier protein -- (L)ACS (long-chain) acyl CoA synthase -- ARF ADP-ribosylation factor -- ARL ARF-like -- AMPK AMP-activated protein kinase -- AVR Avirulence -- cBID cleaved BH3-interacting domain death agonist -- CBL calcineurin B-like -- CDPK calcium-dependent protein kinases -- CoA coenzyme A -- ER endoplasmic reticulum -- FA fatty acid -- FAE fatty acid elongase -- FAS fatty acid synthase -- GNAT GCN5-related N-acetyltransferase -- GPI glycosylphosphatidylinositol -- HBV hepatitis B virus -- Lgt phosphatidylglycerol:prolipoprotein diacylglyceryl transferase -- Lnt (apo)lipoprotein N-acyl transferase -- LPA lysophosphatidic acid -- MyrCoA myristoyl-coenzyme A -- NEFA non-esterified fatty acids -- NMT N-myristoyltransferase -- PBL PBS1-like RLCK -- PA phosphatidic acid -- PE phosphatidylethanolamine -- PEG polyethylene glycol -- PG phosphatidylglycerol -- PM plasma membrane -- RLCK receptor-like cytoplasmic kinase -- RTX Repeat in ToXin class -- TAAT toxin-activating acyl-transferase -- TAG triacylglycerol -- TAMRA tetramethylrhodamine -- TE thioesterase -- TEV tobacco etch virus -- TNF tumor necrosis factor; Lipids -- Periodicals; Lipids -- Periodicals; Lipides -- Périodiques; Lipiden; 572.57
• DOI: 10.1016/j.plipres.2021.101139
• Languages: English
• ISSNs: 0163-7827

Abstract

Abstract: Protein myristoylation is a C14 fatty acid modification found in all living organisms. Myristoylation tags either the N-terminal alpha groups of cysteine or glycine residues through amide bonds or lysine and cysteine side chains directly or indirectly via glycerol thioester and ester linkages. Before transfer to proteins, myristate must be activated into myristoyl coenzyme A in eukaryotes or, in bacteria, to derivatives like phosphatidylethanolamine. Myristate originates through de novo biosynthesis ( e.g., plants), from external uptake ( e.g., human tissues), or from mixed origins ( e.g., unicellular organisms). Myristate usually serves as a molecular anchor, allowing tagged proteins to be targeted to membranes and travel across endomembrane networks in eukaryotes. In this review, we describe and discuss the metabolic origins of protein-bound myristate. We review strategies for in vivo protein labeling that take advantage of click-chemistry with reactive analogs, and we discuss new approaches to the proteome-wide discovery of myristate-containing proteins. The machineries of myristoylation are described, along with how protein targets can be generated directly from translating precursors or from processed proteins. Few myristoylation catalysts are currently described, with only N-myristoyltransferase described to date in eukaryotes. Finally, we describe how viruses and bacteria hijack and exploit myristoylation for their pathogenicity. Highlights: The origins and regulatory role of myristate donors for protein myristoylation are described for each living organism. In vivo protein labeling strategies that take advantage of click chemistry with alkyl or azido analogs are described. We discuss new approaches to the proteome-wide discovery of myristate-containing proteins. We update the catalogue of the main myristoylated proteins together with how they shuttle in different compartments. We discuss how viruses and bacteria exploit myristoylation for their pathogenicity. New catalysts for myristoylation must be discovered soon to advance the field.