Department of Life Sciences and Chemistry, Jacobs University, Bremen, Germany.
Department of Life Sciences and Chemistry, Jacobs University, Bremen, Germany.
Cell Rep. 2018 Jun 5;23(10):3068-3077. doi: 10.1016/j.celrep.2018.05.017.
The murine cytomegalovirus immunoevasin m152/gp40 binds major histocompatibility complex (MHC) class I molecules and retains them in the early secretory pathway by a previously unknown mechanism, preventing antigen presentation to CD8 T cells. We show that retention of class I and of gp40 itself depends on a lumenal linker sequence in gp40. With unbiased co-immunoprecipitation and mass spectrometry, we find that, through this linker, gp40 binds to TMED10/Tmp21/p24δ1, a member of the p24 family of endoplasmic reticulum (ER)/Golgi transmembrane proteins. We show that the C-terminal KKxxx Golgi-to-ER retrieval signal of TMED10 is required for gp40-mediated retention of class I. We thus identify a viral interaction partner of the p24 proteins and their exploitation for viral immune evasion.
鼠巨细胞病毒免疫逃逸蛋白 m152/gp40 通过一种先前未知的机制与主要组织相容性复合体 (MHC) Ⅰ类分子结合，并将其保留在早期分泌途径中，从而阻止抗原呈递给 CD8 T 细胞。我们表明，Ⅰ类分子和 gp40 本身的保留依赖于 gp40 中的腔内连接序列。通过无偏共免疫沉淀和质谱分析，我们发现通过该连接子，gp40 与 TMED10/Tmp21/p24δ1 结合，后者是内质网 (ER)/高尔基体跨膜蛋白 p24 家族的成员。我们表明 TMED10 的 C 末端 KKxxx 高尔基体到内质网回收信号对于 gp40 介导的Ⅰ类分子保留是必需的。因此，我们鉴定了 p24 蛋白的病毒相互作用伙伴，并利用它们进行病毒免疫逃逸。
