Localization of a peripheral membrane protein:: Gβγ targets Gαz

To explore the relative roles of protein-binding partners vs. lipid modifications in controlling membrane targeting of a typical peripheral membrane protein, G alpha(z), we directed its binding partner, beta(gamma), to mislocalize on mitochondria. Mislocalized beta(gamma) directed wildtype G alpha(z) and a palmitate-lacking G alpha(z) mutant to mitochondria but did not alter localization of a G alpha(z) mutant lacking both myristate and palmitate. Thus, in this paradigm, a protein-protein interaction controls targeting of a peripheral membrane protein to the proper compartment. whereas lipid modifications stabilize interactions of proteins with membranes and with other proteins.