Graduate School of Natural Science and Technology, Gifu University, Gifu, 501-1193, Japan.
Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Suita, 565-0871, Japan; Laboratory of Molecular Immunology, Immunology Frontier Research Center (IFReC), Osaka University, Suita, 565-0871, Japan.
Carbohydr Res. 2024 Nov;545:109285. doi: 10.1016/j.carres.2024.109285. Epub 2024 Oct 2.
N-Glycan branching critically regulates glycoprotein functions and is involved in various diseases. Among the glycosyltransferases involved in N-glycan branching is the human N-acetylglucosaminyltransferase-IV (GnT-IV) family, which has four members: GnT-IVa, GnT-IVb, GnT-IVc, and GnT-IVd. GnT-IVa and GnT-IVb have glycosyltransferase activity that generates the type-2 diabetes-related β1,4-GlcNAc branch on the α1,3-Man arm of N-glycans, whereas GnT-IVc and GnT-IVd do not. Recently, this enzyme family was found to have a unique lectin domain in the C-terminal region, which is essential for enzyme activity toward glycoprotein substrates but not toward free N-glycans. Furthermore, interaction between the lectin domain of GnT-IV and N-glycan attached to GnT-IV enables self-regulation of GnT-IV activity, indicating that the lectin domain plays a unique and pivotal role in the regulation of GnT-IV activity. In this review, we summarize the GnT-IV family's biological functions, selectivity for glycoprotein substrates, and regulation of enzymatic activity, with a focus on its unique C-terminal lectin domain.
N-糖基化分支对糖蛋白功能至关重要，并与各种疾病有关。参与 N-糖基化分支的糖基转移酶包括人类 N-乙酰氨基葡萄糖基转移酶-IV（GnT-IV）家族，该家族有四个成员：GnT-IVa、GnT-IVb、GnT-IVc 和 GnT-IVd。GnT-IVa 和 GnT-IVb 具有糖基转移酶活性，可在 N-糖链的α1,3-Man 臂上生成与 2 型糖尿病相关的β1,4-GlcNAc 分支，而 GnT-IVc 和 GnT-IVd 则没有。最近，人们发现该酶家族在 C 末端区域具有独特的凝集素结构域，该结构域对于糖蛋白底物的酶活性是必需的，但对于游离 N-糖链则不是必需的。此外，GnT-IV 的凝集素结构域与附着在 GnT-IV 上的 N-糖链之间的相互作用能够自我调节 GnT-IV 的活性，表明该凝集素结构域在调节 GnT-IV 活性方面发挥着独特而关键的作用。在这篇综述中，我们总结了 GnT-IV 家族的生物学功能、对糖蛋白底物的选择性以及酶活性的调节，重点介绍了其独特的 C 末端凝集素结构域。
