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Updated: May 31, 2026
06:45
Transmembrane Domain Oligomerization Propensity determined by ToxR Assay
Published on: May 26, 2011
Transmembrane Domain Oligomerization and Intracellular Domain-Lipid Interaction Oppositely Modulates OX40 Receptor
Wenge Dong1, Wanqi Wang1, Yin Yang1
1State Key Laboratory of Elemento-Organic Chemistry and Frontiers Science Center for New Organic Matter, College of Chemistry, Nankai University, Tianjin 300071, China.
Journal of the American Chemical Society
|May 29, 2026
Summary
The OX40 receptor
Area of Science:
- Immunology and Molecular Biology
- Biophysics and Chemical Biology
Background:
- The OX40 (CD134) receptor is a key target for antitumor and autoimmune treatments.
- Its precise signaling pathways are not fully understood, hindering therapeutic development.
Purpose of the Study:
- To investigate the role of the OX40 transmembrane domain (TMD) and intracellular domain (ICD) in receptor signaling.
- To elucidate the association mechanisms between OX40 and downstream TRAF2 in a near-native membrane environment.
Main Methods:
- Utilized a combination of fluorine nuclear magnetic resonance (19F NMR), double electron-electron resonance (DEER), and isothermal titration calorimetry (ITC).
- Studied the OX40 receptor within simulated near-native membrane environments.
Main Results:
- Demonstrated that OX40 transmembrane domain oligomerization enhances TRAF2 association.
- Showed that intracellular domain-lipid interactions inhibit TRAF2 association.
- Revealed opposing modulatory effects of TMD oligomerization and ICD-lipid interactions on TRAF2 binding to the acid-rich sequence (ARS) motif.
Conclusions:
- Uncovered a novel regulatory mechanism for OX40 signaling involving a balance between activation and inhibition.
- OX40 signal transduction is dynamically controlled by a tug-of-war between lipid-ICD inhibition and TMD oligomerization-driven activation.
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