9GVQ

MUC5AC mucin amino acids 28 to 1483

Summary for 9GVQ

• Entry DOI: 10.2210/pdb9gvq/pdb
• Related: 9GVJ
• EMDB information: 51639
• Descriptor: Mucin-5AC, CALCIUM ION, COPPER (II) ION (3 entities in total)
• Functional Keywords: mucin, lung, filament, polymer, disulfide, protein fibril
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 4
• Total formula weight: 629057.87

Authors

Haberman, M.,Kamyshinsky, R.,Fass, D. (deposition date: 2024-09-25, release date: 2024-12-04, Last modification date: 2025-03-19)

Primary citation

Haberman, M.,Kamyshinsky, R.,Reznik, N.,Yeshaya, N.,Khmelnitsky, L.,Plender, E.G.,Eichler, E.E.,Fass, D.
MUC5AC filaments illuminate the structural diversification of respiratory and intestinal mucins.
Proc.Natl.Acad.Sci.USA, 122:e2419717122-e2419717122, 2025

PubMed Abstract: Secreted mucins are multimegadalton glycoprotein polymers that share the function of protecting mucosal tissues but diversified for activities in different organs of the body. Structural studies of secreted mucins are complicated by the enormous sizes, flexibility, and complex supramolecular assembly modes of these glycoproteins. The two major respiratory mucins are MUC5AC and MUC5B. Here, we present structures of a large amino-terminal segment of MUC5AC in the form of helical filaments. These filaments differ from filamentous and tubular structures observed previously for the intestinal mucin MUC2 and the partial mucin homolog VWF. Nevertheless, the MUC5AC helical filaments support the proposed mechanism, based on MUC2 and VWF, for how noncovalent interactions between mucin monomers guide disulfide crosslinking to form polymers. The high-resolution MUC5AC structures show how local and limited changes in amino acid sequence can profoundly affect higher-order assembly while preserving the overall folds and polymerization activity of mucin glycoproteins. Differences in supramolecular assembly are likely to be functionally significant considering the divergence of mechanical properties and physiological requirements between respiratory and intestinal mucins. Determining the high-resolution structures of respiratory mucins provides a foundation for understanding the mechanisms by which they clean and protect the lungs. Moreover, the MUC5AC structure enables visualization of the sites of human amino acid sequence variation and disease-associated mutations.

PubMed: 40035770
DOI: 10.1073/pnas.2419717122

Experimental method

ELECTRON MICROSCOPY (3.9 Å)