ArticleThe Journal of biological chemistry2014
Assembly of the respiratory mucin MUC5B: a new model for a gel-forming mucin.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 91 citations in OpenAlex.
- Increased low-molecular-weight mucins in muco-obstructive airway disease limitInfection and immunity · 2026Article
- Mucin 2 and unfolded protein response reshape the mucus barrier in inflammatory bowel disease (Review).Molecular medicine reports · 2026Review
- Simple and accessible methods for quantifying isolated mucins for further evaluation.MethodsX · 2025Article
- Functional divergence of MdpS and MdpS2 reveals mucin-targeting strategies inJournal of oral microbiology · 2025Article
- Emerging cell and molecular targets for treating mucus hypersecretion in asthma.Allergology international : official journal of the Japanese Society of Allergology · 2024Review
- A novel cysteine-rich adaptor protein is required for mucin packaging and secretory granule stability in vivo.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Characterization of MdpS: an in-depth analysis of a MUC5B-degrading protease fromFrontiers in microbiology · 2024Article
- Mucins MUC5AC and MUC5B Are Variably Packaged in the Same and in Separate Secretory Granules.American journal of respiratory and critical care medicine · 2022Article
- Regulated Restructuring of Mucins During Secretory Granule Maturation In Vivo.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- In vivo models of mucin biosynthesis and function.Advanced drug delivery reviews · 2022Review
- The lipophilic cyclic peptide cyclosporin A induces aggregation of gel-forming mucins.Scientific reports · 2022Article
- Mucus and Mucins: The Underappreciated Host Defence System.Frontiers in cellular and infection microbiology · 2022Review
- Human ocular mucins: The endowed guardians of sight.Advanced drug delivery reviews · 2022Review
- Endotoxins Induced ECM-Receptor Interaction Pathway Signal Effect on the Function of MUC2 in Caco2/HT29 Co-Culture Cells.Frontiers in immunology · 2022Article
- Heme Peroxidases at Unperturbed and Inflamed Mucous Surfaces.Antioxidants (Basel, Switzerland) · 2021Review
- Assembly and organization of the N-terminal region of mucin MUC5AC: Indications for structural and functional distinction from MUC5B.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Slimy partners: the mucus barrier and gut microbiome in ulcerative colitis.Experimental & molecular medicine · 2021Review
- Article
- Acidic Submucosal Gland pH and Elevated Protein Concentration Produce Abnormal Cystic Fibrosis Mucus.Developmental cell · 2020Article
- Mucins and the Microbiome.Annual review of biochemistry · 2020Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
Mucins are essential components in mucus gels that form protective barriers at all epithelial surfaces, but much remains unknown about their assembly, intragranular organization, and post-secretion unfurling to form mucus. MUC5B is a major polymeric mucin expressed by respiratory epithelia, and we investigated the molecular mechanisms involved during its assembly. Studies of intact polymeric MUC5B revealed a single high affinity calcium-binding site, distinct from multiple low affinity sites on each MUC5B monomer. Self-diffusion studies with intact MUC5B showed that calcium binding at the protein site catalyzed reversible cross-links between MUC5B chains to form networks. The site of cross-linking was identified in the MUC5B D3-domain as it was specifically blocked by D3 peptide antibodies. Biophysical analysis and single particle EM of recombinant MUC5B N terminus (D1D2D'D3; NT5B) and subdomains (D1, D1-D2, D2-D'-D3, and D3) generated structural models of monomers and disulfide-linked dimers and suggested that MUC5B multimerizes by disulfide linkage between D3-domains to form linear polymer chains. Moreover, these analyses revealed reversible homotypic interactions of NT5B at low pH and in high calcium, between disulfide-linked NT5B dimers, but not monomers. These results enable a model of MUC5B to be derived, which predicts mechanisms of mucin intracellular assembly and storage, which may be common to the other major gel-forming polymeric mucins.
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