Structure of an exophthalmos-producing factor derived from thyrotropin by partial pepsin digestion.
Previously reported experiments (Winand, R.J., and Kohn, L.D. (1970) J. Biol. Chem. 245, 967-975; Kohn, L.D., and Winand, R.J. (1971) J. Biol. Chem 246, 6570-6575) have demonstrated that partial pepsin digestion of bovine thyrotropin preparation yields a fragment of the thyrotropin molecule which is exophthalmogenic but has negligible or no thyroid-stimulating activity. In the present report this exophthalmogenic derivative of the thyrotropin molecule is shown to contain two major polypeptide components with approximate molecular weights of 14,000 and 6,000. Amino acid analyses, carbohydrate analyses, and tryptic digestion experiments indicate that this exophthalmogenic factor is composed of an intact or nearly intact beta subunit of thyrotropin and an NH2-terminal fragment of the alpha subunit of thyrotropin. Neither polypeptide component of the exophthalmogenic factor has the in vivo exophthalmogenic activity of the intact structure. In vitro the intact exophthalmogenic derivative of the thyrotropin molecule can bind to the thyrotropin receptor on thyroid membranes less efficiently than thyrotropin but significantly better than either its own polypeptide components or the alpha or beta subunits of thyrotropin. The exophthalmogenic factor and its parent thyrotropin molecule can stimulate adenylate cyclase activity in retro-orbital tissue membranes from guinea pigs, a mammalian model of exophthalmos; its polypeptide components have little or no such activity.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis; D000818:Animals; D002417:Cattle; D004789:Enzyme Activation / Q000187:drug effects; D005643:Fucose / Q000032:analysis; D005688:Galactosamine / Q000032:analysis; D005690:Galactose / Q000032:analysis; D005944:Glucosamine / Q000032:analysis; D006168:Guinea Pigs; D008358:Mannose / Q000032:analysis; D008970:Molecular Weight; D010434:Pepsin A; D010446:Peptide Fragments / Q000032:analysis; D013972:Thyrotropin / Q000032:analysis* / Q000276:immunology / Q000494:pharmacology
D000596:Amino Acids; D010446:Peptide Fragments; D005643:Fucose; D005688:Galactosamine; D013972:Thyrotropin; D010434:Pepsin A; D000262:Adenylyl Cyclases; D005944:Glucosamine; D008358:Mannose; D005690:Galactose