BOVINE GALLBLADDER MUCIN CONTAINS 2 DISTINCT TANDEM REPEATING SEQUENCES - EVIDENCE FOR SCAVENGER RECEPTOR CYSTEINE-RICH REPEATS

Gall-bladder mucin is a densely glycosylated macromolecule which is th e primary secretory product of the gall-bladder epithelium. It has bee n shown to bind cholesterol and other biliary lipids and to promote ch olesterol crystal nucleation in vitro. In order to understand the mole cular basis for mucin-lipid interactions, bovine gall-bladder mucin cD NAs were identified by expression cloning and were isolated and sequen ced. The nucleotide sequences of these cDNAs revealed two distinct tan dem repeating domains. One of these domains contained a 20-amino acid tandem repeating sequence enriched in threonine, serine and proline. T his sequence was similar to, but not identical with, the short tandem repeating sequences identified previously in other mammalian mucins. T he other domain contained a 127-amino acid tandem repeating sequence e nriched in cysteine and glycine. This repeat displayed considerable se quence similarity to a family of receptor- and ligand-binding proteins containing scavenger receptor cysteine-rich repeats. By analogy with other proteins containing these cysteine-rich repeats, it is possible that, in gall-bladder mucin, this domain serves as a binding site for hydrophobic ligands such as bilirubin, cholesterol and other biliary l ipids.