1hwg
From Proteopedia
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1:2 COMPLEX OF HUMAN GROWTH HORMONE WITH ITS SOLUBLE BINDING PROTEIN
Contents |
Overview
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.
Disease
Known diseases associated with this structure: Growth hormone deficiency OMIM:[139250], Growth hormone deficiency, isolated, type IA OMIM:[139250], Growth hormone deficiency, isolated, type IB OMIM:[139250], Growth hormone deficiency, isolated, type II OMIM:[139250], Increased responsiveness to growth hormone OMIM:[600946], Kowarski syndrome OMIM:[139250], Laron dwarfism OMIM:[600946], Short stature, autosomal dominant, with normal serum growth hormone binding protein OMIM:[600946], Short stature, familial OMIM:[139250], Short stature, idiopathic OMIM:[600946]
About this Structure
1HWG is a Protein complex structure of sequences from Homo sapiens. The following page contains interesting information on the relation of 1HWG with [Growth Hormone]. Full crystallographic information is available from OCA.
Reference
Crystal structure of an antagonist mutant of human growth hormone, G120R, in complex with its receptor at 2.9 A resolution., Sundstrom M, Lundqvist T, Rodin J, Giebel LB, Milligan D, Norstedt G, J Biol Chem. 1996 Dec 13;271(50):32197-203. PMID:8943276
Page seeded by OCA on Thu Mar 20 11:42:22 2008
