Which of the following lipids forms a thioester bond with cysteine?
Distinction between cysteine lipidations clarifies regulation of membrane affinity. S-palmitoylation involves nucleophilic attack of cysteine thiolate on palmitoyl-CoA thioester producing thioester bond between sixteen-carbon saturated palmitate and side chain catalyzed by membrane-integrated DHHC zinc finger enzymes containing conserved Asp-His-His-Cys motif utilizing palmitoyl-CoA donor. This thioester is reversible rapidly cleaved by serine hydrolases APT1, APT2, PPT1 and ABHD17 allowing depalmitoylation cycles controlling localization of HRas trafficking between Golgi and plasma membrane, G-alpha subunits signal termination, synaptic scaffolds PSD-95 and glutamate receptors GluN2A. Hydroxylamine at neutral pH specifically hydrolyzes thioester providing biochemical diagnostic cleavage while thioether and amide resist. N-myristoylation forms stable amide to N-terminal glycine, prenylation forms thioether to C-terminal CAAX cysteine via farnesyltransferase or geranylgeranyltransferase resistant to hydroxylamine. GPI attachment uses amide to ethanolamine. Hence palmitic acid uniquely creates hydroxylamine-labile thioester with cysteine enabling dynamic raft association. Functional assays using hydroxylamine cleavage and metabolic labeling with alkyne palmitate analogues confirm dynamic palmitoylation turnover in living cells.
Ref: Resh, Palmitoylation of Ligands, Receptors and Intracellular Signaling Molecules, Sci STKE 2006.