Voshol H, van Zuylen C W, Orberger G, Vliegenthart J F, Schachner M
Department of Neurobiology, Swiss Federal Institute of Technology, Hönggerberg, CH-8093 Zürich, Switzerland.
J Biol Chem. 1996 Sep 20;271(38):22957-60. doi: 10.1074/jbc.271.38.22957.
The HNK-1 carbohydrate epitope, expressed by many neural recognition molecules, is involved in cell interactions that control cell type-specific neurite outgrowth and regeneration. It is also the target for autoimmune IgM antibodies in demyelinating neuropathies of the peripheral nervous system in humans. Despite its acknowledged importance in cell interactions, the HNK-1 carbohydrate structure, when expressed on glycoproteins, is still unknown. Here, we describe the structure of one of the predominant HNK-1-bearing glycans of bovine P0. The epitope consists of the sulfated trisaccharide SO4-3GlcAbeta1-3Galbeta1-4GlcNAc, attached to the alpha1-6 arm of a diantennary core with a bisecting N-acetylglucosamine. It is the first example of a terminal 3-sulfated glucuronic acid on an asparagine-linked carbohydrate. Because the similarity between the glycoprotein-derived structure and the glycosphingolipids carrying HNK-1 is restricted to the terminal sulfated trisaccharide, we conclude that this element is sufficient for HNK-1 immunoreactivity. Knowledge of the HNK-1 structure on proteins is an important prerequisite for the elucidation of its functional role in development and disease.
许多神经识别分子所表达的HNK-1碳水化合物表位，参与了控制细胞类型特异性神经突生长和再生的细胞相互作用。它也是人类外周神经系统脱髓鞘性神经病中自身免疫性IgM抗体的靶标。尽管其在细胞相互作用中的重要性已得到公认，但糖蛋白上表达的HNK-1碳水化合物结构仍不清楚。在此，我们描述了牛P0主要携带HNK-1聚糖之一的结构。该表位由硫酸化三糖SO4-3GlcAbeta1-3Galbeta1-4GlcNAc组成，连接到具有平分N-乙酰葡糖胺的二天线核心的α1-6臂上。这是天冬酰胺连接的碳水化合物上末端3-硫酸化葡糖醛酸的首个实例。由于糖蛋白衍生结构与携带HNK-1的糖鞘脂之间的相似性仅限于末端硫酸化三糖，我们得出结论，该元件足以产生HNK-1免疫反应性。了解蛋白质上的HNK-1结构是阐明其在发育和疾病中的功能作用的重要前提。
