Interaction of the C-terminal region of the Gγ protein with model membranes

Heterotrimeric G-proteins interact with membranes. They accumulate around membrane receptors and propagate messages to effectors localized in different cellular compartments. G-protein-lipid interactions regulate G-protein cellular localization and activity. Although we recently found that the G beta gamma dimer drives the interaction of G-proteins with nonlamellar-prone membranes, little is known about the molecular basis of this interaction. Here, we investigated the interaction of the C-terminus of the G gamma(2) protein (P gamma-FN) with model membranes and those of its peptide (P gamma) and farnesyl (FN) moieties alone. X-ray diffraction and differential scanning calorimetry demonstrated that P gamma-FN, segregated into P gamma-FN-poor and -rich domains in phosphatidylethanolamine (PE) and phosphatidylserine (PS) membranes. In PE membranes, FN increased the nonlamellar phase propensity. Fourier transform infrared spectroscopy experiments showed that P gamma andP gamma-FN interact with the polar and interfacial regions of PE and PS bilayers. The binding of P gamma-FN to model membranes is due to the FN group and positively charged amino acids near this lipid. On the other hand, membrane lipids partially altered P gamma-FN structure, in turn increasing the fluidity of PS membranes. These data highlight the relevance of the interaction of the C-terminal region of the G gamma protein with the cell membrane and its effect on membrane structure.