Cooperativity in regulation of membrane protein function: phenomenological analysis of the effects of pH and phospholipids

Interaction between membrane proteins and ligands is key to control a wide spectrum of cellular processes. These interactions can provide a cooperative-type regulation of protein function. A wide diversity of proteins, including enzymes, channels, transporters, and receptors show cooperative behavior. The variety of possible ligands is also huge and includes specific molecules or ions that bind to an also specific binding site. In this review, we focus on the interaction of membrane proteins with ligands that present many binding sites, such as protons or membrane phospholipids. The study of the interaction that protons or lipids have with membrane proteins does not always allow a clear and classic mechanistic modeling approach. In this regard we show that, like Hill´s pioneering work on hemoglobin regulation, phenomenological modeling constitutes a powerful tool to describe relevant features of these important systems.