2aew

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{{STRUCTURE_2aew| PDB=2aew | SCENE= }}
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==A model for growth hormone receptor activation based on subunit rotation within a receptor dimer==
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===A model for growth hormone receptor activation based on subunit rotation within a receptor dimer===
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<StructureSection load='2aew' size='340' side='right' caption='[[2aew]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
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{{ABSTRACT_PUBMED_16116438}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2aew]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AEW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2AEW FirstGlance]. <br>
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==Disease==
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</td></tr><tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2aew FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2aew OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2aew RCSB], [http://www.ebi.ac.uk/pdbsum/2aew PDBsum]</span></td></tr>
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[[http://www.uniprot.org/uniprot/GHR_HUMAN GHR_HUMAN]] Defects in GHR are a cause of Laron syndrome (LARS) [MIM:[http://omim.org/entry/262500 262500]]. A severe form of growth hormone insensitivity characterized by growth impairment, short stature, dysfunctional growth hormone receptor, and failure to generate insulin-like growth factor I in response to growth hormone.<ref>PMID:2779634</ref><ref>PMID:8421103</ref><ref>PMID:8504296</ref><ref>PMID:8450064</ref><ref>PMID:8137822</ref><ref>PMID:9024232</ref><ref>PMID:9661642</ref><ref>PMID:9851797</ref><ref>PMID:10870033</ref><ref>PMID:14678285</ref> Defects in GHR may be a cause of idiopathic short stature autosomal (ISSA) [MIM:[http://omim.org/entry/604271 604271]]. Short stature is defined by a subnormal rate of growth.<ref>PMID:7565946</ref>
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<table>
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== Disease ==
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==Function==
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[[http://www.uniprot.org/uniprot/GHR_HUMAN GHR_HUMAN]] Defects in GHR are a cause of Laron syndrome (LARS) [MIM:[http://omim.org/entry/262500 262500]]. A severe form of growth hormone insensitivity characterized by growth impairment, short stature, dysfunctional growth hormone receptor, and failure to generate insulin-like growth factor I in response to growth hormone.<ref>PMID:2779634</ref> <ref>PMID:8421103</ref> <ref>PMID:8504296</ref> <ref>PMID:8450064</ref> <ref>PMID:8137822</ref> <ref>PMID:9024232</ref> <ref>PMID:9661642</ref> <ref>PMID:9851797</ref> <ref>PMID:10870033</ref> <ref>PMID:14678285</ref> Defects in GHR may be a cause of idiopathic short stature autosomal (ISSA) [MIM:[http://omim.org/entry/604271 604271]]. Short stature is defined by a subnormal rate of growth.<ref>PMID:7565946</ref>
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== Function ==
[[http://www.uniprot.org/uniprot/GHR_HUMAN GHR_HUMAN]] Receptor for pituitary gland growth hormone involved in regulating postnatal body growth. On ligand binding, couples to the JAK2/STAT5 pathway (By similarity). The soluble form (GHBP) acts as a reservoir of growth hormone in plasma and may be a modulator/inhibitor of GH signaling. Isoform 2 up-regulates the production of GHBP and acts as a negative inhibitor of GH signaling.
[[http://www.uniprot.org/uniprot/GHR_HUMAN GHR_HUMAN]] Receptor for pituitary gland growth hormone involved in regulating postnatal body growth. On ligand binding, couples to the JAK2/STAT5 pathway (By similarity). The soluble form (GHBP) acts as a reservoir of growth hormone in plasma and may be a modulator/inhibitor of GH signaling. Isoform 2 up-regulates the production of GHBP and acts as a negative inhibitor of GH signaling.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ae/2aew_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Growth hormone is believed to activate the growth hormone receptor (GHR) by dimerizing two identical receptor subunits, leading to activation of JAK2 kinase associated with the cytoplasmic domain. However, we have reported previously that dimerization alone is insufficient to activate full-length GHR. By comparing the crystal structure of the liganded and unliganded human GHR extracellular domain, we show here that there is no substantial change in its conformation on ligand binding. However, the receptor can be activated by rotation without ligand by inserting a defined number of alanine residues within the transmembrane domain. Fluorescence resonance energy transfer (FRET), bioluminescence resonance energy transfer (BRET) and coimmunoprecipitation studies suggest that receptor subunits undergo specific transmembrane interactions independent of hormone binding. We propose an activation mechanism involving a relative rotation of subunits within a dimeric receptor as a result of asymmetric placement of the receptor-binding sites on the ligand.
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==About this Structure==
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Model for growth hormone receptor activation based on subunit rotation within a receptor dimer.,Brown RJ, Adams JJ, Pelekanos RA, Wan Y, McKinstry WJ, Palethorpe K, Seeber RM, Monks TA, Eidne KA, Parker MW, Waters MJ Nat Struct Mol Biol. 2005 Sep;12(9):814-21. Epub 2005 Aug 21. PMID:16116438<ref>PMID:16116438</ref>
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[[2aew]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AEW OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<ref group="xtra">PMID:016116438</ref><references group="xtra"/><references/>
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</div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Adams, J J.]]
[[Category: Adams, J J.]]

Revision as of 02:47, 30 September 2014

A model for growth hormone receptor activation based on subunit rotation within a receptor dimer

2aew, resolution 2.70Å

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