A novel mechanism of TRAF signaling revealed by structural and functional analyses of the TRADD-TRAF2 interaction
A novel mechanism of TRAF signaling revealed by structural and functional analyses of the TRADD-TRAF2 interaction
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DOI：
10.1016/s0092-8674(00)80889-2
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发表时间：
2000-06-23
期刊：
影响因子：
64.5
通讯作者：
Wu, H
中科院分区：
文献类型：
--
作者：
Park, YC;Ye, H;Wu, H
TRAP 蛋白是 TNF 受体超家族的细胞激活、细胞存活和抗凋亡功能的主要介质。它们可以通过与受体直接相互作用或通过衔接蛋白 TRADD 间接相互作用而被招募到激活的 TNF 受体上。我们现在报道了 TRADD-TRAF2 复合物的结构，该复合物与受体-TRAF2 相互作用高度不同。这种相互作用明显更强，我们通过体内信号传导测定表明，TRADD 比直接受体-TRAF2 相互作用更容易启动 TRAF2 信号传导。 TRADD 对 TRAF1 和 TRAF2 具有特异性，可确保招募 cIAP 以直接抑制信号复合物中的 caspase 激活。 TRADD-TRAF2 相互作用更强的亲和力和独特的特异性对于抑制细胞凋亡至关重要，并为扰动 TRAP 募集在敏化细胞死亡诱导中的作用提供了机制基础。
TRAP proteins are major mediators for the cell activation, cell survival, and antiapoptotic functions of the TNF receptor superfamily. They can be recruited to activated TNF receptors either by direct interactions with the receptors or indirectly via the adaptor protein TRADD. We now report the structure of the TRADD-TRAF2 complex, which is highly distinct from receptor-TRAF2 interactions. This interaction is significantly stronger and we show by an in vivo signaling assay that TRAF2 signaling is more readily initiated by TRADD than by direct receptor-TRAF2 interactions. TRADD is specific for TRAF1 and TRAF2, which ensures the recruitment of cIAPs for the direct inhibition of caspase activation in the signaling complex. The stronger affinity and unique specificity of the TRADD-TRAF2 interaction are crucial for the suppression of apoptosis and provide a mechanistic basis for the perturbation of TRAP recruitment in sensitizing cell death induction.