lipidaatio

Lipidaatio, or lipidation, is the covalent attachment of lipid groups to biomolecules, most often proteins. This post-translational modification changes hydrophobicity, enables association with cellular membranes, and can influence localization, stability, trafficking, and interactions.

Common lipidations include N-myristoylation, S-palmitoylation, prenylation, and the attachment of glycosylphosphatidylinositol (GPI) anchors. N-myristoylation adds a myristoyl group to an N-terminal glycine; S-palmitoylation attaches a palmitoyl group to cysteines; prenylation attaches farnesyl or geranylgeranyl groups to C-terminal CaaX motifs; GPI-anchoring attaches a GPI moiety to a protein's C-terminus, anchoring it to the outer leaflet of the membrane.

Enzymes responsible include N-myristoyltransferases (NMT1/2) for myristoylation; DHHC family protein acyltransferases for palmitoylation; farnesyltransferases and geranylgeranyltransferases for prenylation; and GPI transamidase for GPI-anchoring. Reversible palmitoylation is regulated by acyl-protein thioesterases and related enzymes.

Biological roles are diverse. Lipidation promotes membrane targeting and signaling; it can regulate protein stability and interactions. Examples include Src family kinases and many Ras family proteins that require prenylation, and peripheral membrane proteins that rely on myristoylation or palmitoylation for correct localization.

Clinical and research relevance: aberrant lipidation is linked to cancer and neurodegenerative diseases. Inhibitors of prenyltransferases were explored as cancer therapies; palmitoylation is being studied as a drug target. Lipidation is dynamic in many contexts, especially palmitoylation, and is studied using metabolic labeling and mass spectrometry.