Bonifacino J S, Cosson P, Klausner R D
Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, Bethesda, Maryland 20892.
Cell. 1990 Nov 2;63(3):503-13. doi: 10.1016/0092-8674(90)90447-m.
The intracellular fate of T cell antigen receptor (TCR) subunits (alpha beta gamma delta epsilon zeta 2) is determined by their assembly in the endoplasmic reticulum (ER). To study the structural bases for this tight correlation between assembly and intracellular fate, we sought to define the nature of determinants for both ER degradation and subunit assembly within the TCR-alpha chain. We found that a 9 amino acid transmembrane sequence of the TCR-alpha chain, containing 2 critical charged residues, was sufficient to cause ER degradation when placed in the context of the Tac antigen, used here as a reporter protein. CD3-delta assembled with chimeric proteins containing this short transmembrane sequence, and this assembly resulted in abrogation of targeting for ER degradation. Thus, the colocalization of determinants for ER degradation and sites of subunit interactions explains how the fate of some newly synthesized TCR chains can be decided on the basis of their assembly status.
T细胞抗原受体（TCR）亚基（αβγδεζ2）在细胞内的命运取决于它们在内质网（ER）中的组装情况。为了研究组装与细胞内命运之间这种紧密关联的结构基础，我们试图确定TCR-α链中内质网降解和亚基组装的决定因素的性质。我们发现，TCR-α链的一个9个氨基酸的跨膜序列，包含2个关键的带电残基，当置于Tac抗原（此处用作报告蛋白）的背景下时，足以导致内质网降解。CD3-δ与含有这个短跨膜序列的嵌合蛋白组装在一起，这种组装导致内质网降解靶向作用的消除。因此，内质网降解决定因素与亚基相互作用位点的共定位解释了一些新合成的TCR链的命运如何根据它们的组装状态来决定。
