lipidmodified

Lipidmodification, or lipidation, is the covalent attachment of lipid groups to biomolecules, most often to proteins. Molecules bearing such modifications are described as lipidmodified. Lipid modification generally increases hydrophobicity, promotes membrane association, and can influence subcellular localization, trafficking, stability, and protein–protein interactions.

Common forms of lipid modification include N-myristoylation, S-palmitoylation, prenylation, and GPI anchoring. N-myristoylation attaches a myristoyl group to an N-terminal glycine co-translationally, mediated by the enzyme N-myristoyltransferase, and often contributes to membrane targeting and interaction surfaces. S-palmitoylation attaches palmitate to cysteine residues via a thioester bond; it is catalyzed by DHHC palmitoyltransferases and is reversible, allowing dynamic regulation of localization and signaling. Prenylation attaches isoprenoid groups (farnesyl or geranylgeranyl) to C-terminal cysteine in a CaaX motif, performed by farnesyltransferase or geranylgeranyltransferase, followed by proteolysis and methylation; this commonly anchors signaling proteins to membranes. GPI anchoring attaches a glycosylphosphatidylinositol moiety to the C-terminus, producing a protein tethered to the outer leaflet of the plasma membrane.

Other lipid modifications exist, including cholesterol or other lipid adducts in specific proteins or contexts. Functionally, lipidmodification can regulate membrane microdomain localization, protein stability, and interactions that drive signaling pathways. Detection and study rely on biochemical methods and mass spectrometry, as well as metabolic labeling approaches that track lipid incorporation. Dysregulation of lipidmodification is implicated in cancer, neurodegeneration, and infectious diseases, and grafts of lipidation inhibitors are explored as therapeutic strategies.