title: Mapping of the ligand binding domain of the transforming growth factor beta receptor type III by deletion mutagenesis.
abstract: Transforming growth factor beta (TGF-beta) receptor type III is a membrane-anchored proteoglycan that binds TGF-beta via the core protein. We have determined, by deletion mutagenesis of the receptor type III, the minimal essential region of the extracellular domain that is capable of binding TGF-beta. Nine deletion mutants were produced, six of which are expressed on the cell surface and bind TGF-beta. We find that the shortest of these active mutants, which retains only 253 of the 785 amino acids of the extracellular domain, binds TGF-beta with the same affinity as the full-length receptor. These results indicate that the ligand binding domain lies proximal to the transmembrane domain and is functionally independent from the rest of the extracellular domain. We have determined from the mutants that one of the potential glycosaminoglycan attachment sites in the receptor type III is not utilized. Results from the nonglycosylated mutants confirm that the glycosaminoglycan chains are not required for the folding, targeting, and TGF-beta binding activity of the receptor. Moreover, we present evidence for dimerization and multimerization of the receptor.
authors.affiliation: Biotechnology Research Institute, National Research Council Canada, Montreal, PQ.
authors.forename: M C
authors.initials: MC
authors.lastname: Pepin
authors.forename: M
authors.initials: M
authors.lastname: Beauchemin
authors.forename: J
authors.initials: J
authors.lastname: Plamondon
authors.forename: M D
authors.initials: MD
authors.lastname: O'Connor-McCourt
mesh_terms: D000345:Affinity Labels; D000818:Animals; D001667:Binding, Competitive; D002460:Cell Line; D004591:Electrophoresis, Polyacrylamide Gel; D006031:Glycosylation; D008024:Ligands; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion; D014162:Transfection
chemical_list: D000345:Affinity Labels; D008024:Ligands; D018125:Receptors, Transforming Growth Factor beta