Mucus glycoprotein, its biophysical and gel-forming properties

Abstract

The mucus glycoprotein molecules of mildly solubilised mucus have been called 'the first units into solution'. These are strand-like, randomly coiling macromolecules 0.5 to 50M. Dalton in molecular weight. Light scattering shows them to be Kuhn coils of a approximately 1000 A long, thin, linearly repeated segment built on a protein chain of about 1000 amino acids, the presumable gene product synthesized by the cell. Mucus, from all sources, involves this glycosylated (approximately 80% sugar) structural subunit, composed of two parts: a bare peptide part, B, and a heavily glycosylated peptide part, T, containing all the sugar in some 200 O-glycosidically linked side chains. The network required for the rheological functioning of mucus, the mucus gel, is built up of these units. A large number of cysteines occur in the bare protein region B. As the crosslink, therefore, either a direct intermolecular disulfide bond (B to B), or a disulfide bond stabilized lectin protein-to-sugar bond (B to T), is presumed to be involved. There may be two levels of crosslinking. Bonds entered into in nascent mucus may be labile, and a freshly secreted mucus blob swells easily. Later on the links seem to become more stable, no longer exchange with ease and there is little swelling. The gel network in mucus may not be infinite, but only an effectively entangled system of very large molecules. On normally functioning respiratory epithelia, indeed, the network may only be transient. Anything which destroys the bare peptide region, e.g. proteolysis, dissolves the network and yields T-domains. There is at most a side-to-side association of the individual glycoprotein subunits in the network strands and rather few branches. The lectin hypothesis for the crosslink would give the cell very easy control over the structural and rheological properties of the secreted product. In the context of the lectin hypothesis it is proposed that the so-called 'link' protein of intestinal mucus is a degraded part of the B+T subunit, the B part plus some of the adjacent T domain. The 'link' protein would thus contain the lectin and would stay bound until released by thiol reduction.