spalmitoylated

Spalmitoylated refers to proteins that have undergone S-palmitoylation, a reversible lipid modification in which a 16-carbon palmitoyl group is covalently attached to a cysteine residue via a thioester bond. This modification increases the hydrophobic character of the targeted region and promotes association with cellular membranes, influencing protein localization, stability, and trafficking.

The reaction is catalyzed by a family of palmitoyltransferases known as DHHC enzymes, which use palmitoyl-CoA as the acyl donor. In humans, multiple DHHC enzymes exhibit distinct subcellular localizations and substrate specificities, allowing diverse regulatory control over which proteins are palmitoylated and where they associate with membranes. Because the thioester linkage is chemically labile, S-palmitoylation is reversible; depalmitoylation is carried out by acyl-protein thioesterases (notably APT1 and APT2) and other thioesterases such as members of the ABHD family, enabling dynamic cycling of the modification in response to cellular signals.

Sites for S-palmitoylation are typically cysteine residues located within or near membrane-targeting regions of proteins, and the modification can modulate interactions with lipid rafts and other membrane microdomains. Functionally, palmitoylation helps recruit soluble cytosolic proteins to membranes, stabilizes peripheral associations, influences trafficking between organelles, and modulates signaling pathways. Substrates include small GTPases (like Ras family members), receptors, ion channels, and various signaling adaptors.

Detection and study of S-palmitoylation employ methods such as acyl-biotin exchange (ABE), acyl-RAC, and metabolic labeling with palmitate analogs (e.g., 17-ODYA) followed by click chemistry, as well as mass spectrometry to identify modification sites. Misregulation of S-palmitoylation has been linked to cancer, neurological disorders, and metabolic diseases, reflecting its broad role in cell signaling and membrane biology.