Intestinal Gel-Forming Mucins Polymerize by Disulfide-Mediated Dimerization of D3 Domains

摘要: The mucin 2 glycoprotein assembles into a complex hydrogel that protects intestinal epithelia and houses the gut microbiome. A major step in assembly is further multimerization of preformed dimers, thought to produce honeycomb-like arrangement upon expansion. Important open questions are how multiple dimers become covalently linked one another compares with analogous processes related polymers such as respiratory tract mucins hemostasis protein von Willebrand factor. Here we report x-ray crystal structure module, found form dimer by two intersubunit disulfide bonds. calls question current model for assembly, which proposes disulfide-mediated trimerization same module. Key residues making interactions across interface highly conserved orthologs, supporting physiological relevance observed quaternary structure. With knowledge residues, it can be demonstrated many these amino acids also present other factor, indicating stable reported herein likely shared this functionally broad family. module thus reveals manner both factor polymerize, drawing deep structural parallels between macromolecular assemblies critical mucosal vasculature.