Solvent-exposed disulfide bonds in mucins and proteins

Solvent-exposed disulfide bonds in mucins and proteins are critical structural elements that maintain the viscoelastic properties of the mucus gel layer. Mucins, such as MUC5AC and MUC5B, are large glycoproteins that polymerize through these disulfide bridges formed between cysteine-rich domains (PMID: 24841279, PMID: 31524139). In pathological conditions like cystic fibrosis and chronic obstructive pulmonary disease (COPD), the mucus becomes hyperviscous due to excessive cross-linking and oxidative stress, leading to airway obstruction (PMID: 24841279, PMID: 25643341). These specific disulfide bonds are termed solvent-exposed because they are accessible to exogenous reducing agents, making them a viable therapeutic target (PMID: 34010543). Mucolytic drugs, most notably N-acetylcysteine (NAC), act by providing a free thiol group that participates in a disulfide-sulfhydryl exchange reaction (PMID: 24841279, PMID: 31524139). This process breaks the interchain cross-links, effectively reducing the viscosity and elasticity of the mucus to facilitate its clearance from the respiratory tract (PMID: 31199916).

Other names

Mucin disulfide bridgesExtracellular disulfide bondsMucin cross-linksInterchain disulfide bonds

Reduction of disulfide bonds via thiol-disulfide exchange, converting polymer-linking bridges into free sulfhydryl groups to decrease mucus viscosity.