autopalmitoylation

Autopalmitoylation is the process by which a protein acquires a palmitoyl group (a 16-carbon fatty acid) on itself. The term is most often used in the study of palmitoyltransferases, particularly the DHHC family, where the enzyme forms an acyl-enzyme intermediate by transferring a palmitoyl group from palmitoyl-CoA to a cysteine residue within its own catalytic DHHC motif. This autopalmitoylation step can be a prerequisite for subsequent transfer of the palmitoyl group to substrate proteins, although in some cases autopalmitoylation can occur without a substrate present.

Mechanistically, the palmitoyl group is transferred to a catalytic cysteine, creating a thioester linkage on the enzyme. This modification can contribute to the enzyme’s activity, stability, or membrane association and often primes the enzyme to catalyze palmitoylation of other targets. The extent and regulatory significance of autopalmitoylation vary among DHHC enzymes and can depend on the lipid environment, cellular conditions, and the availability of palmitoyl-CoA.

Detection and study of autopalmitoylation employ methods such as acyl-biotin exchange, hydroxylamine cleavage assays, metabolic labeling with alkyne-palmitate followed by click chemistry, and mass spectrometry to identify modified residues. These approaches help distinguish enzyme autopalmitoylation from the palmitoylation of substrates.

Biological relevance of autopalmitoylation lies in its influence on protein localization, membrane targeting, and interactions that govern trafficking and signaling. Aberrant regulation of DHHC autopalmitoylation and broader palmitoylation pathways has been implicated in various diseases, making it an area of ongoing research. See also protein palmitoylation and DHHC palmitoyltransferases.