Phosphatidic acid: an electrostatic/hydrogen-bond switch?

Phosphatidic acid (PA) has been shown to be an important bioactive lipid that is specifically recognized by various proteins. As such, it plays a crucial role in cellular signaling in all eukaryotes. An important determinant for PA’s role in its diverse functions is its anionic headgroup that resides very close to the hydrophobic interior of the lipid bilayer. In this chapter, we describe a new model, the electrostatic/hydrogen-bond switch that describes PA’s ionization properties and its specific interaction with proteins. Furthermore, we will allude to the broader implications of the model for all phosphomonoester moieties found in biological compounds. Recent data in support of the model, as well as biological predictions arising from it, are also discussed.