Posttranslational modification of proteins with fatty acids in platelets

Direct modification of proteins by fatty acid can occur as cotranslational N-myristoylation of an N-terminal glycine residue or as posttranslational thioesterification of cysteine residue(s). Platelets provide an excellent model system for studying the posttranslational type of modification in the absence of active protein synthesis and in the absence of protein synthesis-related protein modifications with lipids. Using this model system it was shown that thioesterification of proteins with fatty acid is less specific for palmitate than it was thought earlier and that other saturated, mono- and even polyunsaturated long chain fatty acids can also participate. The chain length and the extent of unsaturation of the protein-linked fatty acid moiety can, very likely, modulate hydrophobic protein-membrane lipid and protein-protein interactions. CD9, HLA class I glycoprotein, glycoproteins Ib, IX and IV, P-selectin and alpha subunits of G proteins have been demonstrated unequivocally as S-fatty acid acylated platelet proteins.