The transmembrane anchor of the T-cell antigen receptor beta chain contains a structural determinant of pre-Golgi proteolysis.
The transmembrane anchor of the T-cell antigen receptor beta chain contains a structural determinant of pre-Golgi proteolysis.
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T 细胞抗原受体 β 链的跨膜锚包含高尔基体前蛋白水解的结构决定因素。
DOI：
10.1091/mbc.1.12.907
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发表时间：
1990
期刊：
影响因子：
--
通讯作者：
Terhorst,C
中科院分区：
文献类型：
--
作者：
Wileman,T;Carson,GR;Shih,FF;Concino,MF;Terhorst,C
对T细胞抗原受体（TCR）的研究表明，内质网或与之密切相关的细胞器可以选择性地保留和降解膜蛋白。TCR的六个亚基（α、β、δ）中只有三个亚基（α、β、δ）对蛋白水解敏感，这一观察结果表明，不稳定蛋白质内的结构特征标志着它们的降解。TCR β链在内质网中被降解，在这项研究中，我们已经开始定义使其易于蛋白水解的蛋白质结构域。实验表明，该蛋白的跨膜锚和短的5个氨基酸的胞质尾含有一个显性的蛋白水解决定簇。当这些残基从β链上去除时，蛋白质变得对蛋白水解具有抗性。即使所得到的β链的胞外域缺乏跨膜锚，它也不会被细胞分泌，而是保留在内质网中。我们的结论是，保留在内质网单独不会导致降解。结果表明，蛋白质的膜锚内的结构特征使β链易于蛋白水解。这通过用TCR β链的膜锚替换白细胞介素2（IL 2）受体（一种在分泌途径内稳定的蛋白质）的膜锚来证实。未修饰的IL 2受体被有效地转运到细胞表面，并且“减锚”构建体被定量地分泌到培养基中。当IL 2受体的膜锚被TCR β链的膜所取代时，嵌合体不能到达高尔基体并迅速降解。
Studies with the T-cell antigen receptor (TCR) have shown that the endoplasmic reticulum, or an organelle closely associated with it, can retain and degrade membrane proteins selectively. The observation that only three (alpha, beta, and delta) of the six (alpha beta gamma delta epsilon zeta) subunits of the TCR are susceptible to proteolysis implies that structural features within the labile proteins mark them for degradation. The TCR beta chain is degraded in the endoplasmic reticulum, and, in this study, we have started to define the domains of the protein that make it susceptible to proteolysis. The experiments show that the transmembrane anchor and short five-amino-acid cytoplasmic tail of the protein contain a dominant determinant of proteolysis. When these residues were removed from the beta chain, the protein became resistant to proteolysis. Even though the resulting ectodomain of the beta chain lacked a transmembrane anchor, it was not secreted by cells and was retained in the endoplasmic reticulum. We conclude that retention in the endoplasmic reticulum alone does not lead to degradation. The results suggest that structural features within the membrane anchor of the protein predispose the beta chain to proteolysis. This was confirmed by replacing the membrane anchor of the interleukin 2 (IL2) receptor, a protein that was stable within the secretory pathway, with that of the TCR beta chain. The unmodified IL2 receptor was transported efficiently to the surface of cells, and an "anchor minus" construct was secreted quantitatively into the culture media. When the membrane anchor of the IL2 receptor was replaced with that of the TCR beta chain, the chimera was unable to reach the Golgi apparatus and was degraded rapidly.