2pfi

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[[Image:2pfi.jpg|left|200px]]<br /><applet load="2pfi" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="2pfi, resolution 1.60&Aring;" />
 
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'''Crystal structure of the cytoplasmic domain of the human chloride channel ClC-Ka'''<br />
 
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==Overview==
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==Crystal structure of the cytoplasmic domain of the human chloride channel ClC-Ka==
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The cytoplasmic domains of ClC chloride channels and transporters are ubiquitously found in eukaryotic family members and have been suggested to be involved in the regulation of ion transport. All cytoplasmic ClC domains share a conserved scaffold that contains a pair of CBS motifs. Here we describe the structure of the cytoplasmic component of the human chloride channel ClC-Ka at 1.6 A resolution. The structure reveals a dimeric organization of the domain that is unusual for CBS motif containing proteins. Using a biochemical approach combining mutagenesis, crosslinking, and analytical ultracentrifugation, we demonstrate that the interaction interface is preserved in solution and that the distantly related channel ClC-0 likely exhibits a similar structural organization. Our results reveal a conserved interaction interface that relates the cytoplasmic domains of ClC proteins and establish a structural relationship that is likely general for this important family of transport proteins.
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<StructureSection load='2pfi' size='340' side='right'caption='[[2pfi]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2pfi]] 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=2PFI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2PFI FirstGlance]. <br>
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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]] 1.6&#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=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene></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=2pfi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pfi OCA], [https://pdbe.org/2pfi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2pfi RCSB], [https://www.ebi.ac.uk/pdbsum/2pfi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2pfi ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/CLCKA_HUMAN CLCKA_HUMAN] Defects in CLCNKA are a cause of Bartter syndrome type 4B (BS4B) [MIM:[https://omim.org/entry/613090 613090]. A digenic, recessive disorder characterized by impaired salt reabsorption in the thick ascending loop of Henle with pronounced salt wasting, hypokalemic metabolic alkalosis, and varying degrees of hypercalciuria. Bartter syndrome type 4B is associated with sensorineural deafness.<ref>PMID:18310267</ref> <ref>PMID:15044642</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/CLCKA_HUMAN CLCKA_HUMAN] Voltage-gated chloride channel. Chloride channels have several functions including the regulation of cell volume; membrane potential stabilization, signal transduction and transepithelial transport. May be important in urinary concentrating mechanisms.
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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/pf/2pfi_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=2pfi ConSurf].
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<div style="clear:both"></div>
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==Disease==
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==See Also==
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Known disease associated with this structure: Bartter syndrome, type 4, digenic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=602024 602024]]
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*[[Ion channels 3D structures|Ion channels 3D structures]]
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== References ==
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==About this Structure==
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<references/>
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2PFI is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=IOD:'>IOD</scene> and <scene name='pdbligand=CL:'>CL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PFI OCA].
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__TOC__
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</StructureSection>
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==Reference==
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The structure of the cytoplasmic domain of the chloride channel ClC-Ka reveals a conserved interaction interface., Markovic S, Dutzler R, Structure. 2007 Jun;15(6):715-25. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17562318 17562318]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Dutzler, R.]]
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[[Category: Dutzler R]]
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[[Category: Markovic, S.]]
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[[Category: Markovic S]]
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[[Category: CL]]
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[[Category: IOD]]
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[[Category: cystathionine beta synthetase (cbs) domains containing protein]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:28:57 2008''
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Current revision

Crystal structure of the cytoplasmic domain of the human chloride channel ClC-Ka

PDB ID 2pfi

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