Domain swapping of death domain superfamily: Alternative strategy for dimerization.

The role of death domain (DD) protein-mediated inter-protein interactions in cell death and immune cell signaling have been extensively investigated as they are tentative targets for therapeutic interventions and are involved in signal transduction. Structural studies, especially those involving the recent advanced cryo-electron microscopy, indicated that the DD superfamily proteins can assemble into different forms of oligomers, including homo and heterodimer, honey comb-like circular oligomer, and helical filament via three types of interactions, namely type I, type II, and type III. Recently, several structural reports indicated that domain swapping-mediated dimerization of the DD superfamily proteins might be an alternative oligomerization strategy in this family of protein interacting domains. In this review, all the binding strategies associated with the DD superfamily are summarized with a special focus on the novel domain swapping mechanism.