Repulsive Backbone-Backbone Interactions Modulate Access to Specific and Unspecific Binding Sites on Surface-Bound Mucins.

Mucin glycoproteins are the matrix-forming key components of mucus, the innate protective barrier protecting us from pathogenic attack. However, this barrier is constantly challenged by mucin-degrading enzymes, which tend to target anionic glycan chains such as sulfate groups and sialic acid residues. Here, we demonstrate that the efficiency of both unspecific and specific binding of small molecules to mucins is reduced when sulfate groups are enzymatically removed from mucins; this is unexpected because neither of the specific mucin-binding partners tested here targets these sulfate motifs on the mucin glycoprotein. Based on simulation results obtained from a numerical model of the mucin macromolecule, we propose that anionic motifs along the mucin chain establish intramolecular repulsion forces which maintain an elongated mucin conformation. In the absence of these repulsive forces, the mucin seems to adopt a more compacted structure, in which the accessibility of several binding sites is restricted. Our results contribute to a better understanding on how different glycans contribute to the broad spectrum of functions mucin glycoproteins have.