School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Korea.
BMB Rep. 2011 Jun;44(6):369-74. doi: 10.5483/BMBRep.2011.44.6.369.
MHC-I molecules play a critical role in immune surveillance against viruses by presenting peptides to cytotoxic T lymphocytes. Although the mechanisms by which MHC-I molecules assemble and acquire peptides in the ER are well characterized, how MHC-I molecules traffic to the cell surface remains poorly understood. To identify novel proteins that regulate the intracellular transport of MHC-I molecules, MHC-I-interacting proteins were isolated by affinity purification, and their identity was determined by mass spectrometry. Among the identified MHC-I-associated proteins was Tmp21, the human ortholog of yeast Emp24p, which mediates the ER-Golgi trafficking of a subset of proteins. Here, we show that Tmp21 binds to human classical and non-classical MHC-I molecules. The Tmp21-MHC-I complex lacks Β(2)-microglobulin, and the number of the complexes is increased when free MHC-I heavy chains are more abundant. Taken together, these results suggest that Tmp21 is a novel protein that preferentially binds to Β(2)-microglobulin-free MHC-I heavy chains.
MHC-I 分子通过将肽呈递给细胞毒性 T 淋巴细胞，在针对病毒的免疫监视中发挥着关键作用。尽管 MHC-I 分子在 ER 中组装和获取肽的机制已得到很好的描述，但 MHC-I 分子如何转运到细胞表面仍知之甚少。为了鉴定新的蛋白质来调节 MHC-I 分子的细胞内转运，我们通过亲和纯化分离了 MHC-I 相互作用蛋白，并通过质谱确定了它们的身份。在鉴定出的 MHC-I 相关蛋白中，Tmp21 是人源酵母 Emp24p 的同源物，它介导了一组蛋白质的 ER-Golgi 转运。在这里，我们表明 Tmp21 与人类经典和非经典 MHC-I 分子结合。Tmp21-MHC-I 复合物缺乏 Β(2)-微球蛋白，当游离 MHC-I 重链更丰富时，复合物的数量会增加。综上所述，这些结果表明 Tmp21 是一种新型蛋白，它优先与 Β(2)-微球蛋白游离的 MHC-I 重链结合。
