1HWG

1:2 COMPLEX OF HUMAN GROWTH HORMONE WITH ITS SOLUBLE BINDING PROTEIN

Summary for 1HWG

• Entry DOI: 10.2210/pdb1hwg/pdb
• Descriptor: GROWTH HORMONE, GROWTH HORMONE BINDING PROTEIN (3 entities in total)
• Functional Keywords: cytokine, hormone, receptor, hematopoietic, complex (hormone-receptor), complex (hormone-receptor) complex, complex (hormone/receptor)
• Biological source: Homo sapiens (human); More
• Cellular location: Secreted: P01241; Cell membrane; Single-pass type I membrane protein. Isoform 2: Cell membrane; Single-pass type I membrane protein. Growth hormone-binding protein: Secreted: P10912
• Total number of polymer chains: 3
• Total formula weight: 76715.27

Authors

Sundstrom, S.M.,Lundqvist, T. (deposition date: 1996-11-13, release date: 1997-11-19, Last modification date: 2024-11-20)

Primary citation

Sundstrom, M.,Lundqvist, T.,Rodin, J.,Giebel, L.B.,Milligan, D.,Norstedt, G.
Crystal structure of an antagonist mutant of human growth hormone, G120R, in complex with its receptor at 2.9 A resolution.
J.Biol.Chem., 271:32197-32203, 1996

PubMed Abstract: Human growth hormone binds two receptor molecules and thereby induces signal transduction through receptor dimerization. At high concentrations, growth hormone acts as an antagonist because of a large difference in affinities at the respective binding sites. This antagonist action can be enhanced further by reducing binding in the low affinity binding site. A growth hormone antagonist mutant Gly-120 --> Arg, has been crystallized with its receptor as a 1:1 complex and the crystal structure determined at 2.9 A resolution. The 1:1 complex is remarkably similar to the native growth hormone-receptor 1:2 complex. A comparison between the two structures reveals only minimal differences in the conformations of the hormone or its receptor in the two complexes, including the angle between the two immunoglobulin-like domains of the receptor. Further, two symmetry-related 1:1 complexes in the crystal form a 2:2 complex with a large solvent inaccessible area between two receptor molecules. In addition, we present here a native human growth hormone-human growth hormone-binding protein 1:2 complex structure at 2.5 A resolution. One important difference between our structure and the previously published crystal structure at 2.8 A is revealed. Trp-104 in the receptor, a key residue in the hormone-receptor interaction, has an altered conformation in the low affinity site enabling a favorable hydrogen bond to be formed with Asp-116 of the hormone.

PubMed: 8943276
DOI: 10.1074/jbc.271.50.32197

Experimental method

X-RAY DIFFRACTION (2.5 Å)