A domain in TNF receptors that mediates ligand-independent receptor assembly and signaling
A domain in TNF receptors that mediates ligand-independent receptor assembly and signaling
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DOI：
10.1126/science.288.5475.2351
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发表时间：
2000-06-30
期刊：
影响因子：
56.9
通讯作者：
Lenardo, MJ
中科院分区：
文献类型：
--
作者：
Chan, FKM;Chun, HJ;Lenardo, MJ
60和80千道尔顿肿瘤坏死因子受体（TNFR）胞外区的保守结构域被鉴定为介导受体三聚体的特异性配体非依赖性组装。该前配体结合组装结构域（PLAD）在物理上不同于与配体形成主要接触的结构域，但对于结合TNF-α并介导信号传导的TNFR复合物的组装是必要的和足够的。TNFR超家族的其他成员，包括TRAIL受体1和CD 40，显示出类似的同型关联。因此，TNFR和相关受体似乎作为预先形成的复合物发挥作用，而不是作为配体结合后寡聚化的单个受体亚基。
A conserved domain in the extracellular region of the 60- and 80-kilodalton tumor necrosis factor receptors (TNFRs) was identified that mediates specific Ligand-independent assembly of receptor trimers. This pre-ligand-binding assembly domain (PLAD) is physically distinct from the domain that forms the major contacts with ligand, but is necessary and sufficient for the assembly of TNFR complexes that bind TNF-alpha and mediate signaling. Other members of the TNFR superfamily, including TRAIL receptor 1 and CD40, show similar homotypic association. Thus, TNFRs and related receptors appear to function as preformed complexes rather than as individual receptor subunits that oligomerize after ligand binding.