Non-symmetrical structural behavior of a symmetric protein: the case of homo-trimeric TRAF2 (tumor necrosis factor-receptor associated factor 2)

The oligomeric state of TRAF2 (tumor necrosis factor-receptor associated factor 2), a TNF (tumor necrosis factor) receptor-associated factor, is crucial for membrane binding and probably plays a fundamental role in regulating the protein function in vivo. In this study we have combined molecular dynamics with the protein contact network approach to characterize the interaction of the three identical subunits of TRAF2. The average structure obtained after a 225 ns simulation reveals that two clusters of different size are formed, one of which includes almost completely two subunits, while the third monomer appears to be more independent. This picture is also confirmed by the estimated average number of inter-subunit contacts and by the comparison of side chains mobility in each monomer. The analysis of equilibrium pressure-induced dissociation measurements supports such findings, indicating that the dimeric-monomeric (2 + 1) might be prevalent with respect to the trimeric configuration, especially in the case of more diluted samples. These findings suggest that the formation of monomeric species, which is crucial for the formation of intra-luminal vesicles, might depend on preferential asymmetric interactions among the three subunits.