小柯机器人

以色列魏兹曼科学研究所Deborah Fass研究组取得最新进展。他们揭示粘蛋白和冯·威兰布兰德因子聚合物的组装机理。相关论文发表在2020年10月7日出版的《细胞》杂志上。

他们提出肠道粘蛋白MUC2的综合结构分析。他们的发现揭示了共同的机制，通过该机制，血液凝固，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。具体地说，冷冻电镜和晶体结构显示了富二硫键和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，一个密集的O-糖基化粘蛋白域在MUC2中起组织作用。粘蛋白组装机制及其对止血的适应性为合理操纵屏障功能和凝血提供了基础。

据悉，空气和食物的摄入会导致呼吸道和肠道遭受物理和生物危害。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冯·威兰布兰德因子保护着这些多样系统中的脆弱细胞层。结肠粘蛋白还可以容纳和喂养肠道微生物组。

附：英文原文

Title: Assembly Mechanism of Mucin and von Willebrand Factor Polymers

Author: Gabriel Javitt, Lev Khmelnitsky, Lis Albert, Lavi Shlomo Bigman, Nadav Elad, David Morgenstern, Tal Ilani, Yaakov Levy, Ron Diskin, Deborah Fass

Issue&Volume: 2020-10-07

Abstract: 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.

DOI: 10.1016/j.cell.2020.09.021

Source: https://www.cell.com/cell/fulltext/S0092-8674(20)31162-4