2bec

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[[Image:2bec.gif|left|200px]]<br /><applet load="2bec" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="2bec, resolution 2.7&Aring;" />
 
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'''Crystal structure of CHP2 in complex with its binding region in NHE1 and insights into the mechanism of pH regulation'''<br />
 
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==Overview==
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==Crystal structure of CHP2 in complex with its binding region in NHE1 and insights into the mechanism of pH regulation==
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The plasma membrane Na+/H+ exchangers (NHE) require calcineurin B homologous protein (CHP) as an obligatory binding partner for ion transport. Here, we report the first crystal structure of CHP (CHP2 isoform) in complex with its binding domain in NHE1. We show that the cytoplasmic alpha-helix of NHE1 is inserted into the hydrophobic cleft formed by N- and C-lobes of CHP2 and that the size and shape of this crevice together with hydrogen bond formation at multiple positions assure a high degree of specificity for interaction with NHE members. Structure-based mutagenesis revealed the importance of hydrophobic interactions between CHP/NHE1 for the function of NHE1. Furthermore, the crystal structure shows the existence of a protruding CHP-unique region, and deletion of this region in CHP2 inhibited the NHE1 activity by inducing the acidic shift of intracellular pH dependence, while preserving interaction with NHE1. These findings suggest that CHP serves as an obligatory subunit that is required both for supporting the basic activity and regulating the pH-sensing of NHE1 via interactions between distinct parts of these proteins.
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<StructureSection load='2bec' size='340' side='right'caption='[[2bec]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
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== Structural highlights ==
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==About this Structure==
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<table><tr><td colspan='2'>[[2bec]] 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=2BEC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2BEC FirstGlance]. <br>
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2BEC is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=YT3:'>YT3</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BEC OCA].
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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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=YT3:YTTRIUM+(III)+ION'>YT3</scene></td></tr>
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==Reference==
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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=2bec FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bec OCA], [https://pdbe.org/2bec PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2bec RCSB], [https://www.ebi.ac.uk/pdbsum/2bec PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2bec ProSAT]</span></td></tr>
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Crystal structure of CHP2 complexed with NHE1-cytosolic region and an implication for pH regulation., Ammar YB, Takeda S, Hisamitsu T, Mori H, Wakabayashi S, EMBO J. 2006 Jun 7;25(11):2315-25. Epub 2006 May 18. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16710297 16710297]
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/CHP2_HUMAN CHP2_HUMAN] Functions as an integral cofactor in cell pH regulation by controlling plasma membrane-type Na(+)/H(+) exchange activity. Binds to and activates SLC9A1/NHE1 in a serum-independent manner, thus increasing pH and protecting cells from serum deprivation-induced death. Also plays a role in the regulation of cell proliferation and tumor growth by increasing the phosphatase activity of PPP3CA in a calcium-dependent manner. Activator of the calcineurin/NFAT signaling pathway. Involved in the cytoplasmic translocation of the transcription factor NFATC3 to the nucleus.<ref>PMID:12226101</ref> <ref>PMID:18815128</ref>
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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/be/2bec_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/main_output.php?pdb_ID=2bec ConSurf].
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<div style="clear:both"></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]]
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[[Category: Protein complex]]
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[[Category: Large Structures]]
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[[Category: Ammar, Y Ben.]]
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[[Category: Ben Ammar Y]]
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[[Category: Hisamitsu, T.]]
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[[Category: Hisamitsu T]]
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[[Category: Mori, H.]]
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[[Category: Mori H]]
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[[Category: Takeda, S.]]
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[[Category: Takeda S]]
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[[Category: Wakabayashi, S.]]
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[[Category: Wakabayashi S]]
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[[Category: YT3]]
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[[Category: calcineurin-homologous protein]]
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[[Category: calcium-binding protein]]
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[[Category: nhe1 regulating protein]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:36:52 2008''
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Current revision

Crystal structure of CHP2 in complex with its binding region in NHE1 and insights into the mechanism of pH regulation

PDB ID 2bec

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