lipidificazione

Lipidificazione, known in English as lipidation, refers to the covalent attachment of fatty acid chains or other lipid moieties to proteins, peptides, or small molecules. This post‑translational modification changes the localization, stability, and activity of the target. The process commonly involves the enzymatic activation of a fatty acid by acyl‑CoA synthases, followed by transfer to specific residues such as cysteine, serine, or lysine through enzymes belonging to the acyltransferase or palmitoyl‑transferase families. In eukaryotes, the most studied form is the addition of a palmitoyl group to cysteine residues (S‑palmitoylation), which reversibly anchors proteins to cell membranes.

Lipidization serves several cellular functions. It can mediate membrane association, thereby dictating subcellular trafficking and signaling events. For instance, the small GTPase Ras is farnesylated and then palmitoylated to localize to the plasma membrane where it participates in growth factor signaling. Lipidation also influences protein stability by protecting proteins from proteasomal degradation or targeting them to specific organelles. In immune cells, the lipidated adaptor protein MyD88 is necessary for Toll‑like receptor signaling. Additionally, lipidation of peptides can modulate their antimicrobial activity or receptor binding affinity.

Defects in lipidation pathways are linked to diseases. Mutations in the gene encoding the protein farnesyltransferase cause achondrogenesis, a severe skeletal dysplasia. Abnormal palmitoylation of the amyloid precursor protein is implicated in Alzheimer’s disease. Synthetic analogs of lipidated proteins are explored as therapeutics, for example, drug delivery vehicles that mimic viral fusion peptides. Research continues to uncover novel lipidated proteins and enzymes, expanding our understanding of the dynamic regulation of cell signaling, membrane biology, and disease mechanisms.