Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China; National Clinical Research Center for Obstetrics and Gynecology (Peking University Third Hospital), Beijing 100191, China; Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing 100191, China; Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing 100191, China.
Department of Orthopedics, First Hospital of China Medical University, Shenyang 110001, China.
Biomed Pharmacother. 2022 Apr;148:112685. doi: 10.1016/j.biopha.2022.112685. Epub 2022 Feb 8.
The post-translational glycosylation of proteins by O-linked α-mannose is conserved from bacteria to humans. Due to advances in high-throughput mass spectrometry-based approaches, a variety of glycoproteins are identified to be O-mannosylated. Various proteins with O-mannosylation are involved in biological processes, providing essential necessity for proper growth and development. In this review, we summarize the process and regulation of O-mannosylation. The multi-step O-mannosylation procedures are quite dynamic and complex, especially when considering the structural and functional inspection of the involved enzymes. The widely studied O-mannosylated proteins in human include α-Dystroglycan (α-DG), cadherins, protocadherins, and plexin, and their aberrant O-mannosylation are associated with many diseases. In addition, O-mannosylation also contributes to diverse functions in lower eukaryotes and prokaryotes. Finally, we present the relationship between O-mannosylation and gut microbiota (GM), and elucidate that O-mannosylation in microbiome is of great importance in the dynamic balance of GM. Our study provides an overview of the processes of O-mannosylation in mammalian cells and other organisms, and also associated regulated enzymes and biological functions, which could contribute to the understanding of newly discovered O-mannosylated glycoproteins.
蛋白质的 O-连接α-甘露糖基化是从细菌到人类都保守的翻译后糖基化过程。由于高通量质谱技术的进步，各种糖蛋白被鉴定为 O-甘露糖化。具有 O-甘露糖化的各种蛋白质参与生物过程，为正常生长和发育提供了必要的条件。在这篇综述中，我们总结了 O-甘露糖化的过程和调控。多步骤的 O-甘露糖化过程非常动态和复杂，特别是在考虑涉及的酶的结构和功能检查时。在人类中广泛研究的 O-甘露糖化蛋白包括α-肌营养不良聚糖（α-DG）、钙粘蛋白、原钙粘蛋白和神经丛蛋白，它们异常的 O-甘露糖化与许多疾病有关。此外，O-甘露糖化也有助于低等真核生物和原核生物的多种功能。最后，我们介绍了 O-甘露糖化与肠道微生物群（GM）之间的关系，并阐明了微生物组中的 O-甘露糖化在 GM 的动态平衡中具有重要意义。我们的研究提供了哺乳动物细胞和其他生物体中 O-甘露糖化过程的概述，以及相关的调节酶和生物学功能，这有助于理解新发现的 O-甘露糖化糖蛋白。
