Structure of the MUC5AC VWD3 assembly responsible for the formation of net-like mucin polymers.

IF 6.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

EMBO Reports Pub Date : 2025-03-01 Epub Date: 2025-02-27 DOI:10.1038/s44319-025-00395-8

Sergio Trillo-Muyo, Anna Ermund, Gunnar C Hansson

引用次数: 0

Abstract

Gel-forming mucins MUC5AC and MUC5B constitute the main structural component of the mucus in the respiratory system. Secreted mucins interact specifically with each other and other molecules giving mucus specific properties. We determined the cryoEM structures of the wild type D3 assembly of the human MUC5AC mucin and the structural single nucleotide polymorphisms (SNP) variants Arg996Gln and Arg1201Trp that affect intermolecular interactions. Our structures explain the MUC5AC N-terminal non-covalent oligomerization after secretion. The D3 assembly forms covalent dimers that can appear in two alternative conformations, open and closed, where the closed conformation dimers interact through an arginine-rich loop in the TIL3 domain to form tetramers. Our study provides a model to explain MUC5AC net-like structures and how the two SNPs will affect mucus organization, something that might affect lung and other diseases.

查看原文本刊更多论文

凝胶状粘蛋白 MUC5AC 和 MUC5B 是呼吸系统粘液的主要结构成分。分泌的粘蛋白相互之间以及与其他分子之间具有特殊的相互作用，从而赋予了粘液特殊的性质。我们测定了人类 MUC5AC 粘蛋白野生型 D3 组装的冷冻电镜结构，以及影响分子间相互作用的结构单核苷酸多态性（SNP）变异 Arg996Gln 和 Arg1201Trp。我们的结构解释了 MUC5AC N 端在分泌后的非共价寡聚化。D3 组装形成共价二聚体，可以开放和封闭两种构象出现，其中封闭构象的二聚体通过 TIL3 结构域中的富精氨酸环相互作用形成四聚体。我们的研究提供了一个模型来解释 MUC5AC 网状结构，以及这两个 SNPs 将如何影响粘液的组织，这可能会影响肺部和其他疾病。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

EMBO Reports 生物-生化与分子生物学

CiteScore

11.20

自引率

1.30%

发文量

267

审稿时长

1 months

期刊介绍： EMBO Reports is a scientific journal that specializes in publishing research articles in the fields of molecular biology, cell biology, and developmental biology. The journal is known for its commitment to publishing high-quality, impactful research that provides novel physiological and functional insights. These insights are expected to be supported by robust evidence, with independent lines of inquiry validating the findings. The journal's scope includes both long and short-format papers, catering to different types of research contributions. It values studies that: Communicate major findings: Articles that report significant discoveries or advancements in the understanding of biological processes at the molecular, cellular, and developmental levels. Confirm important findings: Research that validates or supports existing knowledge in the field, reinforcing the reliability of previous studies. Refute prominent claims: Studies that challenge or disprove widely accepted ideas or hypotheses in the biosciences, contributing to the correction and evolution of scientific understanding. Present null data: Papers that report negative results or findings that do not support a particular hypothesis, which are crucial for the scientific process as they help to refine or redirect research efforts. EMBO Reports is dedicated to maintaining high standards of scientific rigor and integrity, ensuring that the research it publishes contributes meaningfully to the advancement of knowledge in the life sciences. By covering a broad spectrum of topics and encouraging the publication of both positive and negative results, the journal plays a vital role in promoting a comprehensive and balanced view of scientific inquiry.