Abstract
Abstract
Tumor necrosis factor receptor‐associated factor 2 (TRAF2) is a key adaptor in TNF receptor‐signaling that operates as a trimeric assembly. Here we investigate the structural and functional properties of a TRAF2 construct spanning the trimerization and receptor‐binding domains (TRAF2‐NC, residues 266–501). According to SAXS data, under physiological conditions, TRAF2‐NC preserves a stable trimeric structure with signs of conformational flexibility. Conversely, in a mildly acidic environment (pH 5.7), the protein adopts a less compact and more heterogeneous conformation. In this condition, fluorescence energy transfer measurements reveal an increased membrane‐binding propensity in the presence of ganglioside GM1. Together, these results indicate that TRAF2 oligomerization is modulated by pH‐dependent conformational changes, suggesting that increased structural flexibility and partial exposure of hydrophobic regions facilitate membrane association under stress conditions, and providing a mechanistic link between structural dynamics and TRAF2 function.