TRADD participates in various receptor signaling pathways and plays vital roles in many biological activities, including cell survival and apoptosis, in different cellular contexts. TRADD has two distinct functional domains, a TRAF-binding domain at the N-terminus and a death domain (DD) at the C-terminus. The TRAF binding domain of TRADD folds into an α-β plait topology and is mainly responsible for binding TRAF2, while the TRADD-DD can interact with a variety of DD-containing proteins, including receptors and intracellular signaling molecules. After activation of specific receptors such as TNFR1 and DR3, TRADD can bind to the receptor through DD-DD interaction, creating a membrane-proximal platform for the recruitment of downstream molecules to propagate cellular signals. In this review, we highlight recent advances in the studies of the structural mechanism of TRADD adaptor functions for NF-κB activation and apoptosis induction. We also provide suggestions for future structure research related to TRADD-mediated signaling pathways.

TRADD参与各种受体信号传导途径，并且在不同的细胞环境中，在许多生物学活动（包括细胞存活和凋亡）中起着至关重要的作用。TRADD具有两个不同的功能域，即N末端的TRAF结合域和C末端的死亡域（DD）。TRADD的TRAF结合域折叠成α-β褶状拓扑结构，主要负责结合TRAF2，而TRADD-DD可以与多种含DD的蛋白质相互作用，包括受体和细胞内信号分子。在激活特定受体（例如TNFR1和DR3）后，TRADD可以通过DD-DD相互作用与受体结合，从而形成膜近端平台，用于募集下游分子以传播细胞信号。在这篇评论中 我们重点介绍了TRADD衔接子功能对NF-κB激活和凋亡诱导的结构机理研究的最新进展。我们还为与TRADD介导的信号通路相关的未来结构研究提供建议。