MUC5AC filaments illuminate the structural diversification of respiratory and intestinal mucins

• DOI: 10.1073/pnas.2419717122
• Publication Date: 2025-03-04T15:51:56Z
• Authors: Meital Haberman; Roman Kamyshinsky; Nava Reznik; Noa Yeshaya; Lev Khmelnitsky; Elizabeth G. Plender; Evan E. Eichler; Deborah Fass

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