Interplay of Membrane Lipids Differentially Affects Lipid Binding of Phosphatidic Acid Effectors

Abstract

The interaction of phosphatidic acid (PA) with membrane proteins is responsible for a host of cellular functions. To date no PA specific binding domain has been identified. Instead, electrostatic and hydrophobic interactions are likely to work in tandem to regulate PA effector-PA binding. Electrostatic interactions with the PA headgroup are explained by the electrostatic-hydrogen bond switch model, whereas hydrophobic interactions are explained by the negative curvature of (unsaturated) PA. In order to shed light on PA-protein binding we study the interaction of PA with PA effectors in complex lipid mixture, not just phosphatidylcholine (PC) bilayers, using liposome binding assays. Previously we showed that PE differentially affects the binding of PA effectors. We extended this work to now show that the opposite effect is observed in the presence of lyso-phosphocholine (LPC). We also show that under the right conditions diolyeoyl glycerol (DOG) stimulates binding to PA for a well-known and extensively characterized PA-binding protein. PA-effector-PA binding is thus significantly affected by the presence of other membrane lipids. These studies show the need to incorporate other membrane lipids when investigating the interaction of putative PA binding proteins with PA, thereby further our understanding of PA mediated signaling.