View source for 2ht4


==Structure of the Escherichia coli ClC chloride channel Y445W mutant and Fab complex==
<StructureSection load='2ht4' size='340' side='right'caption='[[2ht4]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2ht4]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/"bacillus_coli"_migula_1895 "bacillus coli" migula 1895] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HT4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2HT4 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BR:BROMIDE+ION'>BR</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1ots|1ots]], [[2ht2|2ht2]], [[2ht3|2ht3]], [[2htk|2htk]], [[2htl|2htl]], [[2hlf|2hlf]]</div></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">clcA, eriC ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 "Bacillus coli" Migula 1895])</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2ht4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ht4 OCA], [https://pdbe.org/2ht4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ht4 RCSB], [https://www.ebi.ac.uk/pdbsum/2ht4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ht4 ProSAT]</span></td></tr>
</table>
== Function ==
[[https://www.uniprot.org/uniprot/CLCA_ECOLI CLCA_ECOLI]] Proton-coupled chloride transporter. Functions as antiport system and exchanges two chloride ions for 1 proton. Probably acts as an electrical shunt for an outwardly-directed proton pump that is linked to amino acid decarboxylation, as part of the extreme acid resistance (XAR) response.<ref>PMID:12384697</ref> <ref>PMID:14985752</ref> <ref>PMID:16341087</ref> <ref>PMID:16905147</ref> <ref>PMID:18678918</ref>  
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ht/2ht4_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</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=2ht4 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The Cl-/H+ exchange-transporter CLC-ec1 mediates stoichiometric transmembrane exchange of two Cl- ions for one proton. A conserved tyrosine residue, Y445, coordinates one of the bound Cl- ions visible in the structure of this protein and is located near the intersection of the Cl- and H+ pathways. Mutants of this tyrosine were scrutinized for effects on the coupled transport of Cl- and H+ determined electrophysiologically and on protein structure determined crystallographically. Despite the strong conservation of Y445 in the CLC family, substitution of F or W at this position preserves wild-type transport behavior. Substitution by A, E, or H, however, produces uncoupled proteins with robust Cl- transport but greatly impaired movement of H+. The obligatory 2 Cl-/1 H+ stoichiometry is thus lost in these mutants. The structures of all the mutants are essentially identical to wild-type, but apparent anion occupancy in the Cl- binding region correlates with functional H+ coupling. In particular, as determined by anomalous diffraction in crystals grown in Br-, an electrophysiologically competent Cl- analogue, the well-coupled transporters show strong Br- electron density at the "inner" and "central" Cl- binding sites. However, in the uncoupled mutants, Br- density is absent at the central site, while still present at the inner site. An additional mutant, Y445L, is intermediate in both functional and structural features. This mutant clearly exchanges H+ for Cl-, but at a reduced H+-to-Cl- ratio; likewise, both the central and inner sites are occupied by Br-, but the central site shows lower Br- density than in wild-type (or in Y445F,W). The correlation between proton coupling and central-site occupancy argues that halide binding to the central transport site somehow facilitates movement of H+, a synergism that is not readily understood in terms of alternating-site antiport schemes.

Synergism between halide binding and proton transport in a CLC-type exchanger.,Accardi A, Lobet S, Williams C, Miller C, Dutzler R J Mol Biol. 2006 Sep 29;362(4):691-9. Epub 2006 Aug 2. PMID:16949616<ref>PMID:16949616</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 2ht4" style="background-color:#fffaf0;"></div>

==See Also==
*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Bacillus coli migula 1895]]
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Accardi, A]]
[[Category: Dutzler, R]]
[[Category: Lobet, S]]
[[Category: Miller, C]]
[[Category: Williams, C]]
[[Category: Clc family of channel and transporter]]
[[Category: Fab complex]]
[[Category: H+/cl- antiporter]]
[[Category: Membrane protein]]