Max-Planck Institute for Solid-State Research, DE-70569 Stuttgart, Germany.
Institute of Organic Chemistry, University of Tübingen, DE-72076 Tübingen, Germany.
Science. 2023 Oct 13;382(6667):219-223. doi: 10.1126/science.adh3856. Epub 2023 Oct 12.
Proteins and lipids decorated with glycans are found throughout biological entities, playing roles in biological functions and dysfunctions. Current analytical strategies for these glycan-decorated biomolecules, termed glycoconjugates, rely on ensemble-averaged methods that do not provide a full view of positions and structures of glycans attached at individual sites in a given molecule, especially for glycoproteins. We show single-molecule analysis of glycoconjugates by direct imaging of individual glycoconjugate molecules using low-temperature scanning tunneling microscopy. Intact glycoconjugate ions from electrospray are soft-landed on a surface for their direct single-molecule imaging. The submolecular imaging resolution corroborated by quantum mechanical modeling unveils whole structures and attachment sites of glycans in glycopeptides, glycolipids, N-glycoproteins, and O-glycoproteins densely decorated with glycans.
糖基化的蛋白质和脂质存在于各种生物实体中，在生物功能和功能障碍中发挥作用。目前对这些糖基化生物分子（称为糖缀合物）的分析策略依赖于平均集合的方法，这些方法不能提供在给定分子的各个位点上连接的聚糖的位置和结构的全貌，特别是对于糖蛋白。我们通过使用低温扫描隧道显微镜直接对单个糖缀合物分子进行成像，展示了糖缀合物的单分子分析。电喷雾产生的完整糖缀合物离子在表面上软着陆，以便对其进行直接单分子成像。由量子力学建模证实的亚分子成像分辨率揭示了糖肽、糖脂、N-糖蛋白和 O-糖蛋白中糖的整体结构和连接位点，这些糖蛋白上密集地装饰着聚糖。
