Chan F K, Chun H J, Zheng L, Siegel R M, Bui K L, Lenardo M J
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Science. 2000 Jun 30;288(5475):2351-4. doi: 10.1126/science.288.5475.2351.
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.
在60千道尔顿和80千道尔顿肿瘤坏死因子受体（TNFRs）的细胞外区域中鉴定出一个保守结构域，该结构域介导受体三聚体的特定非配体依赖性组装。这个配体结合前组装结构域（PLAD）在物理上与形成与配体主要接触的结构域不同，但对于结合肿瘤坏死因子-α并介导信号传导的TNFR复合物的组装是必要且充分的。TNFR超家族的其他成员，包括肿瘤坏死因子相关凋亡诱导配体受体1（TRAIL receptor 1）和CD40，也表现出类似的同型缔合。因此，TNFRs和相关受体似乎以预先形成的复合物形式发挥作用，而不是作为配体结合后才寡聚化的单个受体亚基。
