Gut Reaction: How Disulfide Bonding Builds a Healthy Colon

The surface area of a human being is considered to be about 400 square meters, with only about 0.5% of this area represented by skin. Most of the rest of the surface consists of the lung and intestinal epithelium, which unlike the skin, must exchange gasses or nutrients with the environment. This large area of live and active tissue is protected from mechanical and biological threats by a hydrogel coating composed of proteins known as mucins. Mucins are enormous proteins thousands of amino acids in length and heavily modified by carbohydrates. They undergo a step-wise assembly mechanism to produce a network with appropriate properties to allow small molecules to penetrate but to exclude microorganisms. We have discovered that an enzyme that catalyzes formation of disulfide bonds is required for assembly of a structurally intact and functional mucin gel. Mice lacking this enzyme have impaired mucus layers in their colons and are hyper-sensitive to reagents that induce colitis (inflammation of the colon). We will describe current knowledge regarding the production and function of the mucin hydrogel, integrating our recent findings regarding catalyzed disulfide bond formation into the mechanistic assembly model for mucins.