title: An insertion in the human thyrotropin receptor critical for high affinity hormone binding.
abstract: Thyrotropin (TSH), luteinizing hormone (LH), and chorionic gonadotropin (CG) are structurally related glycoprotein hormones, which bind to receptors that share a high degree of sequence similarity. However, comparison of the primary amino acid sequences of the TSH and LH-CG receptors reveals two unique insertions of 8 and 50 amino acids in the extracellular domain of the TSH receptor. The functional significance of these insertions were determined by site-directed mutagenesis. Deletion of the 50-amino acid tract (residues 317 to 366) had no effect on TSH binding or on TSH and thyroid-stimulating immunoglobulin (TSI) biological activities. In contrast, either deletion or substitution of the eight-amino acid region (residues 38 to 45) abolished these activities. This eight-amino acid tract near the amino terminus of the TSH receptor appears to be an important site of interaction for both TSH and TSI.
authors.affiliation: Department of Medicine, Veterans Administration Medical Center, San Francisco, CA 94121.
authors.forename: H L
authors.initials: HL
authors.lastname: Wadsworth
authors.forename: G D
authors.initials: GD
authors.lastname: Chazenbalk
authors.forename: Y
authors.initials: Y
authors.lastname: Nagayama
authors.forename: D
authors.initials: D
authors.lastname: Russo
authors.forename: B
authors.initials: B
authors.lastname: Rapoport
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D002872:Chromosome Deletion; D002999:Clone Cells; D000242:Cyclic AMP / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D015345:Oligonucleotide Probes; D011989:Receptors, Thyrotropin / Q000235:genetics* / Q000378:metabolism; D013972:Thyrotropin / Q000378:metabolism* / Q000494:pharmacology; D014162:Transfection
chemical_list: D015345:Oligonucleotide Probes; D011989:Receptors, Thyrotropin; D013972:Thyrotropin; D000242:Cyclic AMP