palmitoylated

Palmitoylated describes a protein that has undergone palmitoylation, a post-translational modification in which a palmitic acid moiety is covalently attached to a cysteine residue via a thioester bond (S-palmitoylation). While primarily occurring on cysteines, other forms of lipid modification exist, but S-palmitoylation is by far the most common and reversible modification in eukaryotes.

Palmitoylation is catalyzed by a family of membrane-bound protein acyltransferases containing a DHHC (Asp-His-His-Cys) catalytic motif. These enzymes attach palmitate from the cellular pool of acyl-CoA to target proteins. Reversible depalmitoylation is performed by acyl-protein thioesterases, such as APT1 and APT2, and by other thioesterases, allowing dynamic regulation of protein membrane association and signaling.

Palmitoylated proteins often show increased hydrophobicity and membrane affinity, enabling localization to the inner leaflet of the plasma membrane or organelle membranes. This localization influences protein trafficking, stability, interactions, and activity of signaling pathways. The modification can act as a molecular switch, cycling on and off in response to cellular cues.

Examples include members of the Ras and G protein signaling families, and the Hedgehog family, whose activity depends on palmitoylation. Palmitoylation also affects viral proteins and host-pathogen interactions. In many systems, precise palmitoylation patterns control subcellular distribution and signal strength.

Detection and study rely on biochemical and proteomic approaches, such as acyl-biotin exchange (ABE), acyl-resin-assisted capture (Acyl-RAC), metabolic labeling with palmitate analogs (e.g., 17-ODYA) followed by click chemistry, and mass spectrometry-based palmitoyl-proteomics.

Disruptions of palmitoylation have been linked to diseases including cancer, neurological disorders, and developmental abnormalities, reflecting the broad role of this lipid modification in cellular organization and signaling.