The C-terminal dimerization domain of the respiratory mucin MUC5B functions in mucin stability and intracellular packaging before secretion

摘要: Mucin 5B (MUC5B) has an essential role in mucociliary clearance that protects the pulmonary airways. Accordingly, knowledge of MUC5B structure and its interactions with itself other proteins is critical to better understand airway mucus biology improve management lung diseases such as asthma, cystic fibrosis, chronic obstructive disease (COPD). The N-terminal multimerization domain supramolecular organization been previously described, but less known about C-terminal dimerization domain. Here, using cryogenic electron microscopy (cryo-EM) small-angle X-ray scattering (SAXS) analyses recombinant disulfide-linked dimeric we identified asymmetric, elongated twisted structure, a double globular base. We found more resistant disruption than suggesting confers additional stability polymers. Size-exclusion chromatography-multiangle light (SEC-MALS), SPR-based biophysical microscale thermophoresis disclosed no further assembly, did reveal reversible, calcium-dependent between domains were most active at acidic pH, these have intragranular organization. In summary, our results suggest for compaction mucin chains during granular packaging via Our findings stable provides potential target depolymerization remove plugs COPD pathologies.