5ZAZ

Solution structure of integrin b2 monomer tranmembrane domain in bicelle

Summary for 5ZAZ

• Entry DOI: 10.2210/pdb5zaz/pdb
• NMR Information: BMRB: 36165
• Descriptor: Integrin beta-2 (1 entity in total)
• Functional Keywords: integrin b2, protein-lipid interaction, phospholipids, ca2+, cell adhesion
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 5647.62

Authors

Li, H.,Guo, J.,Xu, C. (deposition date: 2018-02-09, release date: 2018-10-17, Last modification date: 2024-05-15)

Primary citation

Guo, J.,Zhang, Y.,Li, H.,Chu, H.,Wang, Q.,Jiang, S.,Li, Y.,Shen, H.,Li, G.,Chen, J.,Xu, C.
Intramembrane ionic protein-lipid interaction regulates integrin structure and function.
PLoS Biol., 16:e2006525-e2006525, 2018

PubMed 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 (Ca2+) 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.

PubMed: 30427828
DOI: 10.1371/journal.pbio.2006525

Experimental method

SOLUTION NMR