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Intramembrane ionic protein-lipid interaction regulates integrin structure and function.


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 ?L?2 (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 ?L?2 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.

SUBMITTER: Guo J 

PROVIDER: S-EPMC6261646 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Intramembrane ionic protein-lipid interaction regulates integrin structure and function.

Guo Jun J   Zhang Youhua Y   Li Hua H   Chu Huiying H   Wang Qinshu Q   Jiang Shutan S   Li Yan Y   Shen Hongbin H   Li Guohui G   Chen Jianfeng J   Xu Chenqi C  

PLoS biology 20181114 11


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 phospholipi  ...[more]

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