1hwg
From Proteopedia
(New page: 200px<br /> <applet load="1hwg" size="450" color="white" frame="true" align="right" spinBox="true" caption="1hwg, resolution 2.5Å" /> '''1:2 COMPLEX OF HUMAN...) |
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| - | [[Image:1hwg.gif|left|200px]]<br /> | + | [[Image:1hwg.gif|left|200px]]<br /><applet load="1hwg" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1hwg" size=" | + | |
caption="1hwg, resolution 2.5Å" /> | caption="1hwg, resolution 2.5Å" /> | ||
'''1:2 COMPLEX OF HUMAN GROWTH HORMONE WITH ITS SOLUBLE BINDING PROTEIN'''<br /> | '''1:2 COMPLEX OF HUMAN GROWTH HORMONE WITH ITS SOLUBLE BINDING PROTEIN'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Human growth hormone binds two receptor molecules and thereby induces | + | 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== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1HWG is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The following page contains interesting information on the relation of 1HWG with [[http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb52_1.html Growth Hormone]]. Full crystallographic information is available from [http:// | + | 1HWG is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The following page contains interesting information on the relation of 1HWG with [[http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb52_1.html Growth Hormone]]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HWG OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Lundqvist, T.]] | [[Category: Lundqvist, T.]] | ||
| - | [[Category: Sundstrom, S | + | [[Category: Sundstrom, S M.]] |
[[Category: complex (hormone/receptor)]] | [[Category: complex (hormone/receptor)]] | ||
[[Category: cytokine]] | [[Category: cytokine]] | ||
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[[Category: receptor]] | [[Category: receptor]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:05:33 2008'' |
Revision as of 11:05, 21 February 2008
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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
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