title: Human growth hormone and extracellular domain of its receptor: crystal structure of the complex.
abstract: Binding of human growth hormone (hGH) to its receptor is required for regulation of normal human growth and development. Examination of the 2.8 angstrom crystal structure of the complex between the hormone and the extracellular domain of its receptor (hGHbp) showed that the complex consists of one molecule of growth hormone per two molecules of receptor. The hormone is a four-helix bundle with an unusual topology. The binding protein contains two distinct domains, similar in some respects to immunoglobulin domains. The relative orientation of these domains differs from that found between constant and variable domains in immunoglobulin Fab fragments. Both hGHbp domains contribute residues that participate in hGH binding. In the complex both receptors donate essentially the same residues to interact with the hormone, even though the two binding sites on hGH have no structural similarity. Generally, the hormone-receptor interfaces match those identified by previous mutational analyses. In addition to the hormone-receptor interfaces, there is also a substantial contact surface between the carboxyl-terminal domains of the receptors. The relative extents of the contact areas support a sequential mechanism for dimerization that may be crucial for signal transduction.
authors.affiliation: Department of Protein Engineering, Genentech, Inc., South San Francisco, CA 94080.
authors.forename: A M
authors.initials: AM
authors.lastname: de Vos
authors.forename: M
authors.initials: M
authors.lastname: Ultsch
authors.forename: A A
authors.initials: AA
authors.lastname: Kossiakoff
mesh_terms: D001665:Binding Sites; D003461:Crystallography; D013006:Growth Hormone / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D006860:Hydrogen Bonding; D008958:Models, Molecular; D015394:Molecular Structure; D009154:Mutation; D011986:Receptors, Somatotropin / Q000737:chemistry* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D011986:Receptors, Somatotropin; D013006:Growth Hormone