1. Intramembrane ionic protein–lipid interaction regulates integrin structure and function.
- Author
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Guo, Jun, Zhang, Youhua, Li, Hua, Chu, Huiying, Wang, Qinshu, Jiang, Shutan, Li, Yan, Shen, Hongbin, Li, Guohui, Chen, Jianfeng, and Xu, Chenqi
- Subjects
MEMBRANE proteins ,BIOINFORMATICS ,PHOSPHOLIPIDS ,CALCIUM ions ,INTEGRINS - Abstract
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 lymphocyte function-associated antigen 1 [LFA-1]) regulates transmembrane heterodimer formation and integrin adhesion through ionic interplay with acidic phospholipids and calcium ions (Ca
2+ ) in T cells. The amino group of the conserved Lys ionically interacts with the phosphate group of acidic phospholipids 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. [ABSTRACT FROM AUTHOR]- Published
- 2018
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