Data from: TAPBPR bridges UDP-glucose:glycoprotein glucosyltransferase 1 onto MHC class I to provide quality control in the antigen presentation pathway

Recently we revealed that TAPBPR is a peptide exchange catalyst important for optimal peptide selection by MHC class I molecules. Here we asked if any other co-factors associate with TAPBPR which would explain its effect on peptide selection. We identify an interaction between TAPBPR and UDP-glucose:glycoprotein glucosyltransferase 1 (UGT1), a folding sensor in the calnexin/calreticulin quality control cycle known to regenerate the Glc1Man9GlcNAc2 moiety on glycoproteins. Our results suggest the formation of a multimeric complex, dependent on a conserved cysteine at position 94 in TAPBPR, in which TAPBPR promotes the association of UGT1 with peptide-receptive class I molecules. We reveal that the interaction between TAPBPR and UGT1 facilities the reglucosylation of the glycan on class I, promoting their recognition by calreticulin. Our results suggest that in addition to being a peptide-editor, TAPBPR improves peptide optimisation by promoting peptide-receptive MHC class I molecules to associate with the peptide-loading complex.

本团队近期证实，TAPBPR是一种肽交换催化剂，对主要组织相容性复合体I类（MHC class I）分子的最优肽段选择过程至关重要。本研究旨在探究是否存在其他辅助因子可与TAPBPR结合，以阐明其调控肽段选择的分子机制。本研究鉴定出TAPBPR与UDP-葡萄糖：糖蛋白葡萄糖基转移酶1（UGT1）之间存在特异性相互作用；UGT1是钙连蛋白（calnexin）/钙网蛋白（calreticulin）质量控制循环中的折叠传感器，已知其可在糖蛋白表面再生Glc1Man9GlcNAc2糖基。研究结果显示，TAPBPR依赖自身第94位保守半胱氨酸（cysteine）形成多聚体复合物，在此复合物中TAPBPR可促进UGT1与肽段接纳型MHC class I分子相结合。本研究发现，TAPBPR与UGT1的相互作用可促进MHC class I分子表面聚糖的再葡萄糖基化，进而增强其被钙网蛋白识别的能力。研究结果表明，TAPBPR除作为肽段编辑因子外，还可通过促进肽段接纳型MHC class I分子与肽加载复合物（peptide-loading complex）结合，优化肽段选择过程。