title: The Gbetagamma dimer drives the interaction of heterotrimeric Gi proteins with nonlamellar membrane structures.
abstract: Heterotrimeric G proteins are peripheral membrane proteins that propagate signals from membrane receptors to regulatory proteins localized in distinct cellular compartments. To facilitate signal amplification, G proteins are in molar excess with respect to G protein-coupled receptors. Because G proteins are capable of translocating from membrane to cytosol, protein-lipid interactions play a crucial role in signal transduction. Here, we studied the binding of heterotrimeric G proteins (Galphabetagamma) to model membranes (liposomes) and that of the entities formed upon receptor-mediated activation (Galpha and Gbetagamma). The model membranes used were composed of defined membrane lipids capable of organizing into either lamellar or nonlamellar (hexagonal H(II)) membrane structures. We demonstrated that although heterotrimeric G(i) proteins and Gbetagamma dimers can bind to lipid bilayers of phosphatidylcholine, their binding to membranes was markedly and significantly enhanced by the presence of nonlamellar phases of phosphatidylethanolamine. Conversely, activated G protein alpha subunits showed an opposite membrane binding behavior with a marked preference for lamellar membranes. These results have important consequences in cell signaling. First, the binding characteristics of the Gbetagamma dimer account for the lipid binding behavior and the cellular localization of heterotrimeric G proteins. Second, the distinct protein-lipid interactions of heterotrimeric G proteins, Gbetagamma dimers, and Galpha subunits with membrane lipids explain, in part, their different cellular mobilizations during signaling upon receptor activation. Finally, their differential interactions with lipids suggest an active role of the membrane lipid secondary structure in the propagation of signals through G protein-coupled receptors.
authors.affiliation: Institut Universitari d'Investigació en Ciències de la Salut, Department of Biology, University of the Balearic Islands, Carretera Valldemossa Kilómetro 7.5, E-07122 Palma de Mallorca, Spain.
authors.forename: Oliver
authors.initials: O
authors.lastname: Vögler
authors.forename: Jesús
authors.initials: J
authors.lastname: Casas
authors.forename: Danita
authors.initials: D
authors.lastname: Capó
authors.forename: Tünde
authors.initials: T
authors.lastname: Nagy
authors.forename: Gudrun
authors.initials: G
authors.lastname: Borchert
authors.forename: Gabriel
authors.initials: G
authors.lastname: Martorell
authors.forename: Pablo V
authors.initials: PV
authors.lastname: Escribá
mesh_terms: D000818:Animals; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D019281:Dimerization; D044387:GTP-Binding Protein beta Subunits / Q000737:chemistry / Q000502:physiology*; D044388:GTP-Binding Protein gamma Subunits / Q000737:chemistry / Q000502:physiology*; D020962:Heterotrimeric GTP-Binding Proteins / Q000737:chemistry*; D015151:Immunoblotting; D008051:Lipid Bilayers / Q000737:chemistry; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry; D008081:Liposomes / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008954:Models, Biological; D010713:Phosphatidylcholines / Q000737:chemistry; D011485:Protein Binding; D017433:Protein Structure, Secondary; D021381:Protein Transport; D015398:Signal Transduction; D013696:Temperature
chemical_list: C118981:G-protein Beta gamma; D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; D008051:Lipid Bilayers; D008055:Lipids; D008081:Liposomes; D010713:Phosphatidylcholines; D020962:Heterotrimeric GTP-Binding Proteins