THE STRUCTURE AND HETEROGENEITY OF RESPIRATORY MUCUS GLYCOPROTEINS

Respiratory mucus glycoproteins purified from both "normal" respiratory secretions and sputa of patients with a variety of hypersecretory conditions are high M(r) linear molecules adopting a random coil configuration in solution. Studies on their polydispersity show them to have an M(r) in the range 3 to 32 x 10(6) and a distribution of length from 200 nm to beyond 10-mu-m. These macromolecules are fragmented by reduction of intermolecular disulfide bonds into subunits, with M(r) approximately 2 x 10(6) and length from 200 to 600 nm. Reduction not only cleaves the mucin molecule but opens, presumably by breaking intramolecular disulfide bonds, cryptic "naked" protein regions. Trypsin digestion of subunits yields high M(r) glycopeptides (M(r), 300 to 500,000), presumably by cleavage of the peptide core within the unfolded "naked" protein domains. Respiratory mucus glycoproteins from infected sputum samples are usually heterogeneous in CsCI density gradients, in contrast to those from "normal" tracheobronchial secretions. The former are characterized by the presence of a number of different mucin species, and the basis for the separation of these mucins appears to be the variable presence of sialic acid and sulfate moleties in the oligosaccharide clusters. This heterogeneity may reflect a difference in cellular origin of the mucins and also may be clinically significant.