title: Dimerization of the extracellular domain of the human growth hormone receptor by a single hormone molecule.
abstract: Human growth hormone (hGH) forms a 1:2 complex with the extracellular domain of its receptor-binding protein (hGHbp) as studied by crystallization, size exclusion chromatography, calorimetry, and a previously undescribed fluorescence quenching assay. These and other experiments with protein engineered variants of hGH have led to the identification of the binding determinants for two distinct but adjacent sites on hGH for the hGHbp, and the data indicated that there are two overlapping binding sites on the hGHbp for hGH. Furthermore, the binding of hGH to the hGHbp occurred sequentially; a first hGHbp molecule bound to site 1 on hGH and then a second hGHbp bound to site 2. Hormone-induced receptor dimerization is proposed to be relevant to the signal transduction mechanism for the hGH receptor and other related cytokine receptors.
authors.affiliation: Department of Protein Engineering, Genentech, Inc., South San Francisco, CA 94080.
authors.forename: B C
authors.initials: BC
authors.lastname: Cunningham
authors.forename: M
authors.initials: M
authors.lastname: Ultsch
authors.forename: A M
authors.initials: AM
authors.lastname: De Vos
authors.forename: M G
authors.initials: MG
authors.lastname: Mulkerrin
authors.forename: K R
authors.initials: KR
authors.lastname: Clauser
authors.forename: J A
authors.initials: JA
authors.lastname: Wells
mesh_terms: D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D001665:Binding Sites; D002850:Chromatography, Gel; D013006:Growth Hormone / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D046911:Macromolecular Substances; D008961:Models, Structural; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011487:Protein Conformation; D011986:Receptors, Somatotropin / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D046911:Macromolecular Substances; D011986:Receptors, Somatotropin; D013006:Growth Hormone