One for All, All for One: The Peculiar Dynamics of TNF-Receptor-Associated Factor (TRAF2) Subunits

TNF Receptor-Associated Factor 2 (TRAF2) is a homo-trimer belonging to the TNF-receptor-associated factor family (TRAFs). The TRAF2 oligomeric state is crucial for receptor binding, the interaction with other proteins (involved in the TNFR signaling), and the interaction with biological membranes. In this study, we present a computational analysis of the Molecular Dynamics of TRAF2-C (a truncated and soluble TRAF2 form) to identify patterns in the interactions between the three chains. We have performed a canonical analysis of the motion applied to molecular dynamics starting from the available crystal structure to identify correlated motions in TRAF2 dynamics. We have computed the displacement matrix, providing a frame-by-frame displacement for each residue in the dynamic. We provide the results in terms of the correlation matrix, which represents a detailed map of the correlated motions of residues. Eventually, we computed the so-called dynamical clusters, based on the Principal Component Analysis (PCA) of the motion (displacement) and the k means application on the first two principal components space. The results clearly indicate that, most of the time, two chains move in a strongly correlated motion, while the third chain follows a freer motion. A detailed analysis of the correlation matrix also shows that a few specific interface residues characterize the interaction of the more independent subunit with the other two. These findings suggest that the equilibrium between the trimer and the dissociated species (dimers and monomers) might be finely tuned by controlling a few critical residues in the protein quaternary structure, probably facilitating the regulation of oligomerization and dissociation in vivo.

Automated summary

In this study, computational analysis of the Molecular Dynamics of TRAF2-C was performed to identify patterns in the interactions between the three chains. The results show that two chains exhibit strongly correlated motion, while the third chain follows a freer motion. Detailed analysis of the correlation matrix reveals specific interface residues that characterize the interaction of the more independent subunit with the other two. These findings suggest that a few critical residues in the protein quaternary structure may finely tune the equilibrium between the trimer and the dissociated species, potentially facilitating the regulation of oligomerization and dissociation in vivo.