title: Increased concentration of polyvalent phospholipids in the adsorption domain of a charged protein.
abstract: We studied the adsorption of a charged protein onto an oppositely charged membrane, composed of mobile phospholipids of differing valence, using a statistical-thermodynamical approach. A two-block model was employed, one block corresponding to the protein-affected region on the membrane, referred to as the adsorption domain, and the other to the unaffected remainder of the membrane. We calculated the protein-induced lipid rearrangement in the adsorption domain as arising from the interplay between the electrostatic interactions in the system and the mixing entropy of the lipids. Equating the electrochemical potentials of the lipids in the two blocks yields an expression for the relations among the various lipid fractions in the adsorption domain, indicating a sensitive dependence of lipid fraction on valence. This expression is a result of the two-block picture but does not depend on further details of the protein-membrane interaction. We subsequently calculated the lipid fractions themselves using the Poisson-Boltzmann theory. We examined the dependence of lipid enrichment, i.e., the ratio between the lipid fractions inside and outside the adsorption domain, on various parameters such as ionic strength and lipid valence. Maximum enrichment was found for lipid valence in the range between -3 and -4 in physiological conditions. Our results are in qualitative agreement with recent experimental studies on the interactions between peptides having a domain of basic residues and membranes containing a small fraction of the polyvalent phosphatidylinositol 4,5-bisphosphate (PIP2). This study provides theoretical support for the suggestion that proteins adsorbed onto membranes through a cluster of basic residues may sequester PIP2 and other polyvalent lipids.
authors.affiliation: Department of Biochemistry, George S. Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv 69978, Israel.
authors.forename: Emir
authors.initials: E
authors.lastname: Haleva
authors.forename: Nir
authors.initials: N
authors.lastname: Ben-Tal
authors.forename: Haim
authors.initials: H
authors.lastname: Diamant
mesh_terms: D008051:Lipid Bilayers / Q000737:chemistry*; D008563:Membrane Lipids / Q000737:chemistry*; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000737:chemistry; D010743:Phospholipids / Q000737:chemistry*; D011506:Proteins / Q000737:chemistry*; D055672:Static Electricity; D013499:Surface Properties; D013816:Thermodynamics
chemical_list: D008051:Lipid Bilayers; D008563:Membrane Lipids; D010455:Peptides; D019269:Phosphatidylinositol 4,5-Diphosphate; D010743:Phospholipids; D011506:Proteins