Chemistry

Two Molecular Forces Work Against Each Other to Control Immune Receptor

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This study uses 19F NMR spectroscopy to investigate how OX40, a transmembrane receptor involved in immune response, becomes activated. The researchers discovered that two opposing mechanisms regulate OX40 activation: oligomerization (clustering) of the transmembrane domain promotes activation, while interactions between the intracellular domain and lipid membranes inhibit it. These findings reveal the molecular-level balance that controls this immune receptor's function.


Understanding OX40 activation mechanisms is important for developing immunotherapies, particularly for cancer treatment and autoimmune diseases, as OX40 is a target for therapeutic intervention. The 19F NMR approach demonstrated here could also be applied to study other transmembrane receptors where traditional structural biology methods are challenging.


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Journal of the American Chemical Society
DOI: 10.1021/jacs.6c04461

Source: [ASAP] Transmembrane Domain Oligomerization and Intracellular Domain–Lipid Interaction Oppositely Modulates OX40 Receptor Activation Unveiled by 19F NMR