1hwg: Difference between revisions
New page: left|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" | ||
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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 14:05, 21 February 2008
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1:2 COMPLEX OF HUMAN GROWTH HORMONE WITH ITS SOLUBLE BINDING PROTEIN
OverviewOverview
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.
DiseaseDisease
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 StructureAbout 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.
ReferenceReference
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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