2aew

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{{Seed}}
 
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[[Image:2aew.png|left|200px]]
 
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==A model for growth hormone receptor activation based on subunit rotation within a receptor dimer==
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The line below this paragraph, containing "STRUCTURE_2aew", creates the "Structure Box" on the page.
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<StructureSection load='2aew' size='340' side='right'caption='[[2aew]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[2aew]] is a 2 chain structure with sequence from [https://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 [https://proteopedia.org/fgij/fg.htm?mol=2AEW FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7&#8491;</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2aew FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2aew OCA], [https://pdbe.org/2aew PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2aew RCSB], [https://www.ebi.ac.uk/pdbsum/2aew PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2aew ProSAT]</span></td></tr>
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{{STRUCTURE_2aew| PDB=2aew | SCENE= }}
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/GHR_HUMAN GHR_HUMAN] Defects in GHR are a cause of Laron syndrome (LARS) [MIM:[https://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:[https://omim.org/entry/604271 604271]. Short stature is defined by a subnormal rate of growth.<ref>PMID:7565946</ref>
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== Function ==
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[https://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/initialview03.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/main_output.php?pdb_ID=2aew 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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===A model for growth hormone receptor activation based on subunit rotation within a receptor dimer===
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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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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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The line below this paragraph, {{ABSTRACT_PUBMED_16116438}}, adds the Publication Abstract to the page
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<div class="pdbe-citations 2aew" style="background-color:#fffaf0;"></div>
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(as it appears on PubMed at http://www.pubmed.gov), where 16116438 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_16116438}}
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__TOC__
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</StructureSection>
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==About this Structure==
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2AEW is a 2 chains structure of sequences 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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<ref group="xtra">PMID:16116438</ref><references group="xtra"/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Adams, J J.]]
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[[Category: Large Structures]]
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[[Category: McKinstry, W J.]]
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[[Category: Adams JJ]]
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[[Category: Parker, M W.]]
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[[Category: McKinstry WJ]]
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[[Category: Waters, M J.]]
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[[Category: Parker MW]]
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[[Category: Hormone/growth factor]]
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[[Category: Waters MJ]]
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[[Category: Mechanism]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Feb 18 09:59:38 2009''
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Current revision

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

PDB ID 2aew

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