Lipid Modifications of GTP-Binding Regulatory Proteins
Modification by lipid groups is being increasingly appreciated as a mechanism to promote the interaction of a wide variety of proteins with cell membranes and, in many cases, to impart functional properties to these proteins. There are three basic classes of lipid-modified proteins, although others may exist. The first class are the acylated proteins, which contain probably the most common lipid modification. The lipid group is most often a saturated fatty acyl group, specifically myristoyl (14-carbon) or palmitoyl (16-carbon), and each of these groups are found on defined sites in proteins (Towler et al, 1988; James, and Olson, 1990). The glycosyl phosphatidylinositol (GPI) anchored proteins comprise the second class; these proteins contain the most complex lipid modification from both structural, as well as biosynthetic, standpoints. The modifying group contains both sugar and lipid components, and this modification is confined to a discrete subset of proteins whose ultimate destination is the external face of the cell’s plasma membrane (Doering et al, 1990). Proteins in the third class of modified proteins contain the the most recent lipid modification identified. These so-called prenylated proteins are modified via addition of either the farnesyl (15-carbon) or the geranylgeranyl (20-carbon) isoprenoids to conserved cysteine residue(s) near or at the COOH-terminus of proteins (Casey, 1992; Maltese, 1990). Additionally, most if not all prenylated proteins are subject to further modifications at the COOH-terminus which apparently impart additional membrane-interaction and/or regulatory properties to these proteins. This review will be concerned with protein acylation and prenylation, since these modifications occur on GTP-binding regulatory proteins (G proteins).
KeywordsMembrane Association Lipid Group Metabolic Labelling Lipid Modification Gamma Subunit
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