The death domain of IRAK-1: An oligomerization domain mediating interactions with MyD88, Tollip, IRAK-1, and IRAK-4
The death domain of IRAK-1: An oligomerization domain mediating interactions with MyD88, Tollip, IRAK-1, and IRAK-4
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DOI：
10.1016/j.bbrc.2007.01.104
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发表时间：
2007-03-23
影响因子：
3.1
通讯作者：
Martin, Michael U.
中科院分区：
文献类型：
--
作者：
Neumann, Detlef;Kollewe, Christian;Martin, Michael U.
Toll样/白细胞介素-1受体家族中的配体结合导致细胞内信号传导复合物的募集。IRAK-1，这是中央参与这个复合物，能够同源寡聚化，并结合Tollip和衔接MyD 88和IRAK-4。IRAK-1与MyD 88或Tollip的相互作用由IRAK-1的N-末端部分介导，所述N-末端部分含有在位置66（T66）处具有高度保守的苏氨酸的死亡结构域。将该氨基酸突变为丙氨酸或天冬氨酸稳定了与MyD 88、Tollip和IRAK-4的结合，从而提供了明确的实验证据，即所有这些相互作用均由IRAK-1的死亡结构域介导。IRAK-1的同源寡聚化也由死亡结构域介导，不受T66突变的影响。最后，IRAK-1在T66处的突变不仅允许与信号适配器稳定结合，而且增强了其信号传导能力。(c)2007年爱思唯尔公司All rights reserved.
Ligand binding in the Toll-like/interleukin-1 receptor family results in the recruitment of an intracellular signaling complex. IRAK-1, which is centrally involved in this complex, is able to homo-oligomerize and to bind to Tollip and the adapters MyD88 and IRAK-4. The interactions of IRAK-1 with MyD88 or Tollip are mediated by the N-terminal part of IRAK-1, containing the death domain with the highly conserved threonine at position 66 (T66). Mutation of this amino acid into alanine or aspartic acid stabilized binding to MyD88, Tollip, and IRAK-4, allowing the definitive experimental proof, that all these interactions are mediated by the death domain of IRAK-1. Homo-oligomerization of IRAK-1, which is mediated by the death domain too, is not affected by mutation of T66. Finally, mutation of IRAK-1 at T66 not only allowed stable binding to the signaling adapters, but also enhanced its signaling capacity. (c) 2007 Elsevier Inc. All rights reserved.