Figure 4.

Phosphatidic acid is a pH biosensor. Effector proteins bind PA according to the electrostatic/hydrogen-bond switch mechanism [29]. Electrostatic interactions and hydrogen bonding (green dashed lines) between the primary amines of basic amino acids in the effector and the deprotonated phosphomonoester of PA are shown. A decrease in intracellular pH below the pK_a of PA results in increased protonation of its phosphomonoester, which reduces the strength of electrostatic interactions with the effector, resulting in its dissociation from the membrane.