Intramembrane ionic protein-lipid interaction regulates integrin structure and function

Published: 17-10-2018| Version 3 | DOI: 10.17632/tg2622h9dd.3
Contributor:
Jun Guo

Description

Protein transmembrane domains (TMDs) are generally hydrophobic but our bioinformatics analysis shows that many TMDs contain basic residues at terminal regions. 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. Our work therefore showcases the importance of intramembrane ionic protein-lipid interaction and provides a new mechanism of integrin activation.

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