Dimerization of the Extracellular Domain of the Human Growth Hormone Receptor by a Single Hormone Molecule

• Published in: Science (American Association for the Advancement of Science) Vol. 254; no. 5033; pp. 821 - 825
• Main Authors: Cunningham, Brian C., Ultsch, Mark, de Vos, Abraham M., Mulkerrin, Michael G., Clauser, Karl R., Wells, James A.
• Format: Journal Article
• Language: English
• Published: United States American Society for the Advancement of Science 08-11-1991; American Association for the Advancement of Science; The American Association for the Advancement of Science
• Subjects: Amino Acid Sequence; Antibodies, Monoclonal; Binding Sites; Chemistry; Chromatography, Gel; Cytokine receptors; Dimerization; Fluorescence; Growth Hormone - metabolism; Hormone receptors; Hormones; Humans; Kinetics; Macromolecular Substances; Models, Structural; Molecular Sequence Data; Molecules; Monoclonal antibodies; Mutagenesis, Site-Directed; Physical growth; Protein binding; Protein Conformation; Receptors; Receptors, Somatotropin - genetics; Receptors, Somatotropin - isolation & purification; Receptors, Somatotropin - metabolism; Research Article; Signal transduction; Somatotropin; Somatotropin receptors; Titration
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1948064

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.