TRAF2-TRADD Interaction A Novel Mode of TRAF Signaling

TRAF2-TRADD Interaction A Novel Mode of TRAF Signaling 

The TRAF2-TRADD interaction is mediated by the TRAF domain of TRAF2 and the N-terminal domain of TRADD (TRADD-N). The TRADD-N domain has so far only been found in mammalian TRADD proteins. It folds into an a-/3 sandwich with a four-stranded /3-sheet and six a-helices, each forming one layer of the structure (Park et al, 2000 Tsao et al, 2000) (Fig. 9A). The /3-sheet is entirely anti-parallel and slightly twisted with a strand order of /32, /33, /31, and /34. There are two helices each in the /31-/32 and /3S-/34 crossover connections while the /32-/3S connection is hairpin-like. The remaining two helices (E and F) are near the carboxy-terminus of the domain the loop in between (EF loop) pardy covers one end of the exposed face of the /3-sheet. 

The basic topology of the TRADD-N domain resembles the family of ferredoxin-like a-j3 sandwiches (Orengo and Thornton, 1993), which are often present as domains in larger structures such as the palm domain of 

The trimeric TRAP domain of TRAF2 imposes the threefold symmetry to the stoichiometrically bound TRADD-N (Fig. 9B, C). When viewed from the side of the mushroom-shaped trimeric structure of TRAF2, 

TRADD-N interacts with TRAF2 at the upper rim of the mushroom cap and adds a wing-like structure to the mushroom. The carboxyl terminus of TRADD-N projects up to the membrane-proximal direction of the complex, indicating the possible location of the carboxyl terminal death domain of TRADD. In this orientation, TRADD can be recruited to TNF-R1 via its death domain and forms the central platform for recruiting other signaling molecules such as FADD, RIP and TRAF2 (Fig. 9D). 

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