伴侣(临床)
糖基化
细胞生物学
化学
受体
N-连接糖基化
生物化学
糖蛋白
生物
医学
聚糖
病理
作者
Mengxiao Ma,Ramin Dubey,Annie Jen,Ganesh V. Pusapati,Bharti Singal,Evgenia Shishkova,Katherine A. Overmyer,Valérie Cormier‐Daire,Juliette Fédry,L. Aravind,Joshua J. Coon,Rajat Rohatgi
出处
期刊:Science
[American Association for the Advancement of Science (AAAS)]
日期:2024-11-07
卷期号:386 (6722): 667-672
标识
DOI:10.1126/science.adp7201
摘要
One-fifth of human proteins are N-glycosylated in the endoplasmic reticulum (ER) by two oligosaccharyltransferases, OST-A and OST-B. Contrary to the prevailing view of N-glycosylation as a housekeeping function, we identified an ER pathway that modulates the activity of OST-A. Genetic analyses linked OST-A to HSP90B1, an ER chaperone for membrane receptors, and CCDC134, an ER luminal protein. During its translocation into the ER, an N-terminal peptide in HSP90B1 templates the assembly of a translocon complex containing CCDC134 and OST-A that protects HSP90B1 during folding, preventing its hyperglycosylation and degradation. Disruption of this pathway impairs WNT and IGF1R signaling and causes the bone developmental disorder osteogenesis imperfecta. Thus, N-glycosylation can be regulated by specificity factors in the ER to control cell surface receptor signaling and tissue development.
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