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首页> 外文期刊>Journal of Molecular Biology >Intestinal Gel-Forming Mucins Polymerize by Disulfide-Mediated Dimerization of D3 Domains
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Intestinal Gel-Forming Mucins Polymerize by Disulfide-Mediated Dimerization of D3 Domains

机译：通过二硫化物介导的D3结构域的二聚化聚合肠凝胶形成粘膜

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The mucin 2 glycoprotein assembles into a complex hydrogel that protects intestinal epithelia and houses the gut microbiome. A major step in mucin 2 assembly is further multimerization of preformed mucin dimers, thought to produce a honeycomb-like arrangement upon hydrogel expansion. Important open questions are how multiple mucin 2 dimers become covalently linked to one another and how mucin 2 multimerization compares with analogous processes in related polymers such as respiratory tract mucins and the hemostasis protein von Willebrand factor. Here we report the x-ray crystal structure of the mucin 2 multimerization module, found to form a dimer linked by two intersubunit disulfide bonds. The dimer structure calls into question the current model for intestinal mucin assembly, which proposes disulfide-mediated trimerization of the same module. Key residues making interactions across the dimer interface are highly conserved in intestinal mucin orthologs, supporting the physiological relevance of the observed quaternary structure. With knowledge of the interface residues, it can be demonstrated that many of these amino acids are also present in other mucins and in von Willebrand factor, further indicating that the stable dimer arrangement reported herein is likely to be shared across this functionally broad protein family. The mucin 2 module structure thus reveals the manner by which both mucins and von Willebrand factor polymerize, drawing deep structural parallels between macromolecular assemblies critical to mucosal epithelia and the vasculature. (C) 2019 The Authors. Published by Elsevier Ltd.
机译：粘蛋白2糖蛋白组合成复合水凝胶，保护肠上皮细胞并容纳肠道微生物组。粘蛋白2组件的主要步骤是预制粘蛋白二聚体的进一步多聚化，旨在在水凝胶膨胀时产生蜂窝状的布置。重要的开放问题是多个粘蛋白2二聚体对彼此共价连接，以及粘蛋白2多能量与相关聚合物中的类似方法进行比较，例如呼吸道粘膜和止血蛋白von willebrand因子。在这里，我们报告了粘液2多聚化模块的X射线晶体结构，发现形成由两种梭氢二硫键连接的二聚体。二聚体结构调用质疑肠粘壁组件的当前模型，该模型提出了相同模块的二硫化介导的三聚化。在二聚体界面上进行相互作用的关键残基在肠粘蛋白正轨中高度保守，支持观察到的四元结构的生理相关性。凭借界面残留物的知识，可以证明许多这些氨基酸也存在于其他粘蛋白中和von Willebrand因子中，进一步表明本文报道的稳定二聚体布置可能会在该功能宽的蛋白质中分享。因此，粘蛋白2模块结构揭示了粘蛋白和冯维尔布朗因子聚合的方式，在粘膜上皮和脉管系统之间关键的大分子组件之间绘制深层结构方差。 （c）2019年作者。 elsevier有限公司出版

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