Allosteric disulfide control of ligand binding and endocytosis of KIR2DL4, the natural killer cell receptor for HLA-G.

Allosteric disulfide bond switching in KIR2DL4 regulates HLA-G binding and endocytosis, with the Cys10-Cys28 bond controlling receptor activation in human NK cells.

• Why it matters: Understanding how KIR2DL4's structural features influence HLA-G interaction is crucial for elucidating mechanisms of placental development and maternal-fetal immune tolerance.
• What they did: Researchers used random mutagenesis, mass spectrometry, and in vitro assays to analyze three cysteines in KIR2DL4, revealing that the Cys10-Cys28 disulfide bond acts as an allosteric switch affecting receptor conformation and function.
• The result: The study shows that conversion from an inactive Cys10-Cys28 bond to an active Cys28-Cys74 bond enables HLA-G binding and endocytosis, suggesting disulfide bond dynamics regulate NK cell responses during pregnancy.