Chapter 13 - Lipid modification of proteins

Abstract

Modification of proteins by covalent attachment of lipids has been identified on over 1000 polypeptides and is a key regulator of protein function. Hydrophobic moieties that have been reported to be linked to proteins include fatty acids (myristate, palmitate), isoprenoids (farnesyl, geranylgeranyl), diacylglyceryl lipids (glycosylphosphatidylinositol anchors) as well as cholesterol and phospholipids. This chapter focuses on the biochemistry of lipid modification, the enzymes that catalyse each of these reactions and the effects of lipid modification on protein localisation, structure and function. Cycles of membrane association and dissociation can occur when enzymes remove the lipid-modifying group, or through molecular switches that result in binding and sequestration of the lipid-modifying group. Small molecules that selectively inhibit lipid-modifying enzymes have been developed, and several have shown efficacy for the treatment of human diseases driven by lipidated proteins.