INTERACTION OF THE C-TERMINAL REGION OF THE G-PROTEIN WITH MODEL MEMBRANES

¹ University of the Balearic Islands
² Universidad Miguel Hernández
³ HASYLAB Hamburg

^* To whom correspondence should be addressed. E-mail: francisca.barcelo{at}uib.es.

Submitted on November 15, 2006
Revised on January 14, 2007
Accepted on 19 March 2007

	Abstract

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 dimer drives the interaction of G proteins with non-lamellar prone membranes, little is known about the molecular basis of this interaction. Here, we investigated the interaction of the C-terminus of the G₂ protein (P-FN) with model membranes, and those of its peptide (P) and farnesyl (FN) moieties alone. X-ray diffraction and DSC demonstrated that P-FN, segregated into P-FN-poor and -rich domains in phosphatidylethanolamine (PE) and phosphatidylserine (PS) membranes. In PE membranes, FN increased the non-lamellar phase propensity. FTIR experiments showed that P and P-FN interact with the polar and interfacial regions of PE and PS bilayers. The binding of P-FN to model membranes is due to the farnesyl group and positively charged amino acids near this lipid. On the other hand, membrane lipids partially altered P-FN structure, in turn increasing the fluidity of phosphatidylserine membranes. These data highlight the relevance of the interaction of the C-terminal region of the G protein with the cell membrane, and its effect on membrane structure.

Key Words: C-terminal Ggamma2 protein, membrane structure, phosphatidylethanolamine, phosphatidylserine