Intestinal Mucin Is a Chaperone of Multivalent Copper

Mucus protects the body by many mechanisms, but a role in managing toxic transition metals was not previously known. Here we report that secreted mucins, the major mucus glycoproteins coating the respiratory and intestinal epithelia, are specific copper-binding proteins. Most remarkably, the intestinal mucin, MUC2, has two juxtaposed copper binding sites, one that accommodates Cu2+ and the other Cu1+, which can be formed in situ by reduction with vitamin C. Copper is an essential trace metal because it is a cofactor for a variety of enzymes catalyzing electron transfer reactions, but copper damages macromolecules when unregulated. We observed that MUC2 protects against copper toxicity while permitting nutritional uptake into cells. These findings introduce mucins, produced in massive quantities to guard extensive mucosal surfaces, as extracellular copper chaperones and potentially important players in physiological copper homeostasis.

The Interaction of the Gut Microbiota with the Mucus Barrier in Health and Disease in Human

Glycoproteins are major players in the mucus protective barrier in the gastrointestinal and other mucosal surfaces. In particular the mucus glycoproteins, or mucins, are responsible for the protective gel barrier. They are characterized by their high carbohydrate content, present in their variable number, tandem repeat domains. Throughout evolution the mucins have been maintained as integral components of the mucosal barrier, emphasizing their essential biological status. The glycosylation of the mucins is achieved through a series of biosynthetic pathways processes, which generate the wide range of glycans found in these molecules. Thus mucins are decorated with molecules having information in the form of a glycocode. The enteric microbiota interacts with the mucosal mucus barrier in a variety of ways in order to fulfill its many normal processes. How bacteria read the glycocode and link to normal and pathological processes is outlined in the review.