TRAF trimers form immune signalling networks via RING domain dimerization
TRAF trimers form immune signalling networks via RING domain dimerization
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DOI：
10.1002/1873-3468.14530
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发表时间：
2022-11-25
期刊：
影响因子：
3.5
通讯作者：
Day, Catherine L.
中科院分区：
文献类型：
--
作者：
Das, Anubrita;Foglizzo, Martina;Day, Catherine L.
对于许多炎性细胞因子，引起的反应依赖于衔接蛋白的肿瘤坏死因子受体相关因子（TRAF）家族的募集。所有TRAF蛋白质具有三聚体C-末端TRAF结构域，而在N-末端大多数TRAF具有形成二聚体的RING结构域。TRAF蛋白的N-和C-末端一半的对称性错配意味着当受体聚集时，推测RING二聚体连接TRAF三聚体以形成网络。在这里，使用纯化的TRAF 6蛋白，我们提供了直接的证据支持这一模型，我们表明，TRAF 6三聚体结合Lys 63连接的泛素链，以促进其进行性装配。这项研究提供了关键的证据，支持TRAF三聚体作为信号传导的关键参与者。
For many inflammatory cytokines, the response elicited is dependent on the recruitment of the tumour necrosis factor receptor-associated factor (TRAF) family of adaptor proteins. All TRAF proteins have a trimeric C-terminal TRAF domain, while at the N-terminus most TRAFs have a RING domain that forms dimers. The symmetry mismatch of the N- and C-terminal halves of TRAF proteins means that when receptors cluster, it is presumed that RING dimers connect TRAF trimers to form a network. Here, using purified TRAF6 proteins, we provide direct evidence in support of this model, and we show that TRAF6 trimers bind Lys63-linked ubiquitin chains to promote their processive assembly. This study provides critical evidence in support of TRAF trimers as key players in signalling.