Intramembrane ionic protein-lipid interaction regulates integrin structure and function

Physiological functions of these membrane-snorkeling basic residues are largely unclear. Here we show that a membrane-snorkeling Lys residue in integrin αLβ2 (also known as LFA-1) regulates transmembrane heterodimer formation and integrin adhesion through ionic interplay with acidic phospholipids and Ca2+ in T cells.

The amino group of the conserved Lys ionically interacts with the phosphate group of acidic phospholipid to stabilize αLβ2 transmembrane association, thus keeping the integrin at low-affinity conformation. Intracellular Ca2+ uses its charge to directly disrupt this ionic interaction, leading to the transmembrane separation and the subsequent extracellular domain extension to increase adhesion activity. This Ca2+-mediated regulation is independent on the canonical Ca2+ signaling or integrin inside-out signaling.