Glycosylation is a fundamental cellular process that, in eukaryotes, occurs in the lumen of both the Golgi apparatus and the endoplasmic reticulum. Nucleotide sugar transporters (NSTs) are an essential component of the glycosylation pathway, providing the diverse range of substrates required for the glycosyltransferases. NSTs are linked to several developmental and immune disorders in humans, and in pathogenic microbes they have an important role in virulence. How NSTs recognize and transport activated monosaccharides, however, is currently unclear. Here we present the crystal structure of an NST, the GDP–mannose transporter Vrg4, in both the substrate-free and the bound states. A hitherto unobserved requirement of short-chain lipids in activating the transporter supports a model for regulation within the highly dynamic membranes of the Golgi apparatus. Our results provide a structural basis for understanding nucleotide sugar recognition, and provide insights into the transport and regulatory mechanism of this family of intracellular transporters.

中文翻译：

---

核苷酸糖跨高尔基体膜转运的结构基础

糖基化是一种基本的细胞过程，在真核生物中，它发生在高尔基体和内质网的腔中。核苷酸糖转运蛋白 (NST) 是糖基化途径的重要组成部分，提供糖基转移酶所需的各种底物。NSTs 与人类的几种发育和免疫障碍有关，在病原微生物中，它们在毒力方面发挥重要作用。 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 然而，NST 如何识别和运输活化的单糖，目前尚​​不清楚。在这里，我们展示了 NST 的晶体结构，即 GDP-甘露糖转运蛋白 Vrg4，在无底物和结合状态下。迄今为止未观察到的短链脂质在激活转运蛋白方面的需求支持高尔基体高动态膜内的调节模型。我们的结果为理解核苷酸糖识别提供了结构基础，并提供了对该细胞内转运蛋白家族的转运和调节机制的见解。