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Ionic protein–lipid interactions at the plasma membrane regulate the structure and function of immunoreceptors
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Recently, an invitation review, entitled “Ionic protein–lipid interactions at the plasma membrane regulate the structure and function of immunoreceptors”, by a research group led by Dr. XU Chenqi at Shanghai Institute of Biochemistry and Cell Biology of the Chinese Academy of Sciences was published in Advances in Immunology. The review highlighted the recent progress in the structural and functional regulation of immunoreceptors by ionic protein–lipid interactions at the plasma membrane.
Adaptive lymphocytes express a panel of activating and inhibitory immunoreceptors on the cell surface. Phospholipids are the major components of cell membranes, but they have functional roles beyond forming lipid bilayers. In particular, acidic phospholipids forming microdomains in the plasma membrane can ionically interact with proteins via polybasic sequences, which can have functional consequences for the protein. Researchers have shown in their previous studies that negatively charged acidic phospholipids can interact with positively charged juxtamembrane polybasic regions of immunoreceptors, such as TCR CD3ε, CD28 and IgG-BCR, to regulate protein structure and function.
Furthermore, researchers pay their attention to protein transmembrane domains (TMDs). TMDs are generally hydrophobic but their bioinformatics analysis targeting TMDs shows that about 40% TMDs contain basic residues at terminal regions. Taking the integrin as an example, they 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 calcium ions (Ca2+) in T cells, thus providing a new mechanism of integrin activation. The review reported the recent progress showcasing the importance of both intramembrane and juxtamembrane ionic protein–lipid interactions.
The work was supported by grants from NSFC grants, CAS grants (Strategic Priority Research Program; Facility-based Open Research Program), STSMC, and Fountain-Valley Life Sciences Fund of University of Chinese Academy of Sciences Education Foundation.
Contact:XU Chenqi  cqxu@sibcb.ac.cn


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