Cysteine 230 is essential for the structure and activity of the cytotoxic ligand TRAIL
Cysteine 230 is essential for the structure and activity of the cytotoxic ligand TRAIL
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DOI：
10.1074/jbc.m909721199
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发表时间：
2000-07-07
影响因子：
4.8
通讯作者：
Schneider, P
中科院分区：
文献类型：
--
作者：
Bodmer, JL;Meier, P;Schneider, P
与其他肿瘤坏死因子家族成员不同，细胞毒性配体肿瘤坏死因子相关凋亡诱导配体（TRAIL）/Apo-2L在其受体结合结构域中含有未配对的半胱氨酸残基（Cys（230））。我们发现可溶性重组TRAIL和细胞相关的全长TRAIL的生物学活性都严重依赖于Cys的存在（230）。Cys（230）突变为丙氨酸或丝氨酸强烈影响其杀伤靶细胞的能力。与其受体的结合减少了至少200倍，其三聚体结构的稳定性降低。在重组TRAIL中，发现Cys（230）参与链间二硫键的形成，导致活性差的TRAIL，或者参与在活性的促凋亡形式的TRAIL中每个TRAIL三聚体的一个锌原子的螯合。
Unlike other tumor necrosis factor family members, the cytotoxic ligand tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)/Apo-2L contains an unpaired cysteine residue (Cys(230)) in its receptor-binding domain. Here we show that the biological activity of both soluble recombinant TRAIL and cell-associated, full-length TRAIL is critically dependent on the presence of Cys(230). Mutation of Cys(230) to alanine or serine strongly affected its ability to kill target cells. Binding to its receptors was decreased by at least 200-fold, and the stability of its trimeric structure was reduced. In recombinant TRAIL, Cys(230) was found engaged either in interchain disulfide bridge formation, resulting in poorly active TRAIL, or in the chelation of one zinc atom per TRAIL trimer in the active, pro-apoptotic form of TRAIL.