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

ZERBETTO DE PALMA, GERARDO; RECOULAT ANGELINI, ALVARO A.; VITALI, VICTORIA; GONZÁLEZ FLECHA, F. LUIS.; ALLEVA, KARINA

Biophysical Reviews

Springer

Año: 2023 vol. 15 p. 721 - 731

1867-2450

Interaction between membrane proteins and ligands plays a key role in governing a wide spectrum of cellular processes. Theseinteractions can provide a cooperative-type regulation of protein function. A wide variety of proteins, including enzymes,channels, transporters, and receptors, displays cooperative behavior in their interactions with ligands. Moreover, the ligandsinvolved encompass a vast diversity and include specific molecules or ions that bind to specific binding sites. In this review,our particular focus is on the interaction between integral membrane proteins and ligands that can present multiple “bindingsites”, such as protons or membrane phospholipids. The study of the interaction that protons or lipids have with membraneproteins often presents challenges for classical mechanistic modeling approaches. In this regard, we show that, like Hill’spioneering work on hemoglobin regulation, phenomenological modeling constitutes a powerful tool for capturing essentialfeatures of these systems.