The respiratory and intestinal tracts are exposed to physical and biological hazards accompanying the intake of air and food. Likewise, the vasculature is threatened by inflammation and trauma. Mucin glycoproteins and the related von Willebrand factor guard the vulnerable cell layers in these diverse systems. Colon mucins additionally house and feed the gut microbiome. Here, we present an integrated structural analysis of the intestinal mucin MUC2. Our findings reveal the shared mechanism by which complex macromolecules responsible for blood clotting, mucociliary clearance, and the intestinal mucosal barrier form protective polymers and hydrogels. Specifically, cryo-electron microscopy and crystal structures show how disulfide-rich bridges and pH-tunable interfaces control successive assembly steps in the endoplasmic reticulum and Golgi apparatus. Remarkably, a densely O-glycosylated mucin domain performs an organizational role in MUC2. The mucin assembly mechanism and its adaptation for hemostasis provide the foundation for rational manipulation of barrier function and coagulation.

随着空气和食物的摄入，呼吸道和肠道会受到物理和生物危害。同样，脉管系统也受到炎症和创伤的威胁。粘蛋白糖蛋白和相关的血管性血友病因子保护着这些不同系统中脆弱的细胞层。结肠粘蛋白还容纳并喂养肠道微生物组。在这里，我们对肠道粘蛋白 MUC2 进行了综合结构分析。我们的研究结果揭示了负责凝血、粘膜纤毛清除和肠粘膜屏障的复杂大分子形成保护性聚合物和水凝胶的共同机制。具体来说，冷冻电子显微镜和晶体结构显示了富含二硫键的桥和pH可调界面如何控制内质网和高尔基体中的连续组装步骤。值得注意的是，密集的 O-糖基化粘蛋白结构域在 MUC2 中发挥着组织作用。粘蛋白组装机制及其对止血的适应为合理操纵屏障功能和凝血提供了基础。