Disulfide bonds in mucins and other extracellular proteins

Disulfide bonds in mucins and other extracellular proteins are critical structural elements that maintain the three-dimensional architecture and rheological properties of biological gels, particularly mucus. In the respiratory tract, mucins such as MUC5AC and MUC5B utilize these covalent bonds to form massive, multimeric networks that provide a protective barrier against environmental insults (PubMed: 22407113). However, in chronic inflammatory airway diseases like cystic fibrosis and COPD, an overabundance of these bonds leads to the formation of hyper-viscous mucus that obstructs the airways and promotes infection (NIH: NBK537183). Therapeutic intervention focuses on the chemical reduction of these disulfide bridges using mucolytic agents like N-acetylcysteine. These drugs possess free sulfhydryl groups that participate in thiol-disulfide exchange reactions, effectively breaking the mucin polymers into smaller, less viscous fragments (StatPearls: NBK537183). This process restores the fluid nature of the mucus, facilitating its removal via coughing or ciliary action and improving overall lung function. Beyond the lungs, these bonds are also targets in treating conditions like keratoconjunctivitis sicca, where mucus plugging occurs and requires chemical disruption to maintain ocular surface health (PubMed: 25100537).

Other names

Mucin disulfide bridgesCystine linkages in mucinsExtracellular disulfide cross-linksIntermolecular disulfide bonds

Reduction of intermolecular disulfide bonds through thiol-disulfide exchange, resulting in the cleavage of high-molecular-weight mucin polymers into smaller subunits and a subsequent reduction in mucus viscosity.