This chapter focuses on the covalent attachment of lipids to G proteins, modifications that anchor G-protein subunits to the membrane. Lipidation of G proteins is essential for their ability to propagate signals from cell surface receptors to effectors. Covalent modifications of G-protein subunits play key roles in their function, localization, and regulation. The discovery of ADP-ribosylation of G-protein β subunits by cholera and pertussis toxins provided significant insights into G-protein function. Gα subunits are modified with myristic and/or palmitic acid. N-myristoylation is the addition of myristic acid to a protein at an N-terminal glycine residue exposed after removal of the initiator methionine. All 12 mammalian Gα subunits are prenylated at C-terminal CaaX motifs, where "C" represents the cysteine that is modified by the isoprenoid and "a" represents an aliphatic residue. The amino acid at position "X" specifies if a farnesyl or a geranylgeranyl group is added to the CaaX box cysteine. Gα1, α9, and α11 terminate with serine and are modified by farnesyltransferase. Myristoylation is necessary for the function of Gai subunits. In mammalian cells, loss of myristoylation by mutation of Gly2 results in a cytoplasmic distribution of the protein and failure to couple to effectors and receptors. The membrane-binding function of the myristoyl group is clearly key to its function, but there is debate as to whether the myristoyl group may serve other functions. Prenylation is not required for Gβγdimer formation, however, it enhances the interaction of Gα and Gβγ.
|Title of host publication||Handbook of Cell Signaling, 2/e|
|Number of pages||5|
|State||Published - 2010|