title: Increased pH-sensitivity of protein binding to lipid membranes through the electrostatic-hydrogen bond switch.
abstract: The signaling lipid phosphatidic acid (PA) is believed to interact specifically with membrane-bound globular proteins through a combination of electrostatic interactions and hydrogen bond formation known as the electrostatic-hydrogen bond switch. PA, which adjusts its protonation state according to the ambient pH, is able to regulate protein binding under physiological conditions in a pH-dependent manner. We investigate the question to what extent the electrostatic-hydrogen bond switch contributes to the pH-sensitivity of protein binding. To this end, we propose a theoretical model for the adsorption of a basic protein on a zwitterionic membrane that contains phosphatidic acid as a minor component. Our model is based on an extended continuum Poisson-Boltzmann approach that accounts for zwitterionic lipids, the protonation/deprotonation equilibrium of PA, and the lateral mobility of the lipids in the membrane. The electrostatic-hydrogen bond switch enters as an additional non-electrostatic attractive interaction of deprotonated PA with basic protein residues. For a generic model protein we calculate the adsorption free energy and its pH-dependence. Our results suggest that the electrostatic-hydrogen bond switch not only increases the affinity between PA and the protein but also its sensitivity with respect to changes in pH. That is, the electrostatic-hydrogen bond switch helps enabling the membrane to use physiological pH changes in order to trigger protein adsorption/desorption.
authors: Department of Physics, North Dakota State University, Fargo, ND 58108-6050, USA.
authors: Stephan
authors: S
authors: Loew
authors: Edgar E
authors: EE
authors: Kooijman
authors: Sylvio
authors: S
authors: May
mesh_terms: D000327:Adsorption; D002462:Cell Membrane / Q000737:chemistry* / Q000378:metabolism*; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D010712:Phosphatidic Acids / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D055672:Static Electricity; D013816:Thermodynamics
chemical_list: D008565:Membrane Proteins; D010712:Phosphatidic Acids