Wang X, Simone L C, Tuli A, Solheim J C
Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198-6805, USA.
Int J Immunogenet. 2009 Jun;36(3):183-7. doi: 10.1111/j.1744-313X.2009.00840.x.
Tapasin is a key molecule in the major histocompatibility complex (MHC) class I peptide-loading complex, interacting with several other proteins in the complex. An amino acid substitution at a free cysteine position in tapasin has been shown to disrupt the covalent association of tapasin with ERp57. In this study, we mutated the free cysteine in mouse tapasin, and analysed the effects on the cell surface expression of the mouse MHC class I molecules K(d) and K(b). The C95S substitution in mouse tapasin increased the proportion of open forms relative to folded forms for both types of MHC class I molecules at the cell surface. Furthermore, the C95S substitution resulted in increased association of tapasin with folded K(d). Overall, our studies with these mouse MHC class I allotypes have revealed that the free cysteine 95 in mouse tapasin influences stable expression at the plasma membrane for both MHC class I allotypes, and have shown that tapasin's interaction with folded K(d) is elevated by the C95S substitution in tapasin.
塔帕辛是主要组织相容性复合体（MHC）I类肽装载复合体中的关键分子，它与该复合体中的其他几种蛋白质相互作用。研究表明，塔帕辛中一个游离半胱氨酸位置的氨基酸替换会破坏塔帕辛与内质网蛋白57（ERp57）的共价结合。在本研究中，我们对小鼠塔帕辛中的游离半胱氨酸进行了突变，并分析了其对小鼠MHC I类分子K(d)和K(b)细胞表面表达的影响。小鼠塔帕辛中的C95S替换增加了细胞表面这两种MHC I类分子开放形式相对于折叠形式的比例。此外，C95S替换导致塔帕辛与折叠的K(d)的结合增加。总体而言，我们对这些小鼠MHC I类同种异型的研究表明，小鼠塔帕辛中的游离半胱氨酸95影响这两种MHC I类同种异型在质膜上的稳定表达，并且表明塔帕辛中的C95S替换会提高塔帕辛与折叠的K(d)的相互作用。
