PANCREATIC SPASMOLYTIC POLYPEPTIDE - FIRST 3-DIMENSIONAL STRUCTURE OFA MEMBER OF THE MAMMALIAN TREFOIL FAMILY OF PEPTIDES

Background: The trefoil peptides are a rapidly grow ing family of pept ides, mainly found in the gastrointestinal tract. There is circumstant ial evidence that they stabilize the mucus layer, and may affect the r ate of healing of the mucosal epithelium. Results: We have determined the structure of porcine pancreatic spasmolytic polypeptide (PSP) to 2 .5 Angstrom resolution. The polypeptide contains two trefoil domains. The domain structure is compact, and is composed of a central short an tiparallel beta-sheet with one short helix above and one below it. Thi s is a novel motif. The two domains are related by two-fold symmetry, and each domain contains a cleft. Conclusions: The cleft within each d omain could accommodate a polysaccharide chain, and may therefore be r esponsible for binding mucin glycoproteins. We suggest that PSP may cr oss-link glycoproteins, explain ing its ability to stabilize the mucus layer.