lipidation

Lipidation is a biochemical process in which lipid groups are covalently attached to proteins or peptides. The addition of lipids increases hydrophobicity and typically promotes or modulates membrane association, subcellular localization, stability, and protein–protein interactions. Lipidation encompasses several distinct classes, including fatty acylation, isoprenylation, and glycosylphosphatidylinositol (GPI) anchoring, and can occur during translation (co-translational) or after protein synthesis (post-translational).

The major forms of lipidation include N-myristoylation, S-palmitoylation, and other fatty acylations, as well as prenylation and GPI anchoring. N-myristoylation attaches a myristoyl group to a glycine residue near the N-terminus, typically by N-myristoyltransferase during or shortly after protein synthesis. S-palmitoylation attaches palmitoyl groups to cysteine residues via thioester bonds, a modification that is reversible and dynamically regulated by specific thioesterases. Prenylation adds farnesyl or geranylgeranyl groups to C-terminal CaaX motifs via farnesyltransferase or geranylgeranyltransferase. GPI anchoring attaches a glycosylphosphatidylinositol moiety to the C-terminus of proteins in the endoplasmic reticulum, tethering them to the outer leaflet of the plasma membrane.

Functionally, lipidation controls membrane targeting, localization to signaling platforms, protein stability, and interactions. It is central to the function of many signaling proteins, including Ras and Rho family members, and is subject to regulation through enzymatic synthesis and, for some modifications, reversal. Dysregulation of lipidation is implicated in diseases such as cancer and congenital disorders; therapeutic strategies have targeted lipidation enzymes, with varying clinical outcomes. Detection and analysis of lipidated proteins employ metabolic labeling, acyl-biotin exchange, and mass spectrometry.