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| | <SX load='6rtf' size='340' side='right' viewer='molstar' caption='[[6rtf]], [[Resolution|resolution]] 7.77Å' scene=''> | | <SX load='6rtf' size='340' side='right' viewer='molstar' caption='[[6rtf]], [[Resolution|resolution]] 7.77Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6rtf]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RTF OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6RTF FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6rtf]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RTF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6RTF FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6rtc|6rtc]]</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 7.77Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Slc26a9, mCG_51751 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=6rtf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rtf OCA], [https://pdbe.org/6rtf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6rtf RCSB], [https://www.ebi.ac.uk/pdbsum/6rtf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6rtf ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6rtf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rtf OCA], [http://pdbe.org/6rtf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6rtf RCSB], [http://www.ebi.ac.uk/pdbsum/6rtf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6rtf ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/A0A0R4J0F7_MOUSE A0A0R4J0F7_MOUSE]] DIDS- and thiosulfate- sensitive anion exchanger mediating chloride, sulfate and oxalate transport.[RuleBase:RU362052] | + | [https://www.uniprot.org/uniprot/S26A9_MOUSE S26A9_MOUSE] DIDS- and thiosulfate- sensitive anion exchanger mediating chloride, sulfate and oxalate transport (PubMed:15800055, PubMed:17120765). Mediates chloride/bicarbonate exchange or chloride-independent bicarbonate extrusion thus assuring bicarbonate secretion (PubMed:15800055, PubMed:17120765). May prefer chloride anions and mediate uncoupled chloride anion transport in an alternate-access mechanism where a saturable binding site is alternately exposed to either one or the other side of the membrane (PubMed:31339488).<ref>PMID:15800055</ref> <ref>PMID:17120765</ref> <ref>PMID:31339488</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </SX> | | </SX> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Dutzler, R]] | + | [[Category: Dutzler R]] |
| - | [[Category: Sawicka, M]] | + | [[Category: Sawicka M]] |
| - | [[Category: Walter, J D]] | + | [[Category: Walter JD]] |
| - | [[Category: Anion transporter]]
| + | |
| - | [[Category: Cryo-em]]
| + | |
| - | [[Category: Membrane protein]]
| + | |
| - | [[Category: Membrane protein structure]]
| + | |
| - | [[Category: Single particle]]
| + | |
| - | [[Category: Slc26 family]]
| + | |
| - | [[Category: Transport mechanism]]
| + | |
| Structural highlights
Function
S26A9_MOUSE DIDS- and thiosulfate- sensitive anion exchanger mediating chloride, sulfate and oxalate transport (PubMed:15800055, PubMed:17120765). Mediates chloride/bicarbonate exchange or chloride-independent bicarbonate extrusion thus assuring bicarbonate secretion (PubMed:15800055, PubMed:17120765). May prefer chloride anions and mediate uncoupled chloride anion transport in an alternate-access mechanism where a saturable binding site is alternately exposed to either one or the other side of the membrane (PubMed:31339488).[1] [2] [3]
Publication Abstract from PubMed
The epithelial anion transporter SLC26A9 contributes to airway surface hydration and gastric acid production. Colocalizing with CFTR, SLC26A9 has been proposed as a target for the treatment of cystic fibrosis. To provide molecular details of its transport mechanism, we present cryo-EM structures and a functional characterization of murine Slc26a9. These structures define the general architecture of eukaryotic SLC26 family members and reveal an unusual mode of oligomerization which relies predominantly on the cytosolic STAS domain. Our data illustrates conformational transitions of Slc26a9, supporting a rapid alternate-access mechanism which mediates uncoupled chloride transport with negligible bicarbonate or sulfate permeability. The characterization of structure-guided mutants illuminates the properties of the ion transport path, including a selective anion binding site located in the center of a mobile module within the transmembrane domain. This study thus provides a structural foundation for the understanding of the entire SLC26 family and potentially facilitates their therapeutic exploitation.
Cryo-EM structures and functional characterization of murine Slc26a9 reveal mechanism of uncoupled chloride transport.,Walter JD, Sawicka M, Dutzler R Elife. 2019 Jul 24;8. pii: 46986. doi: 10.7554/eLife.46986. PMID:31339488[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Xu J, Henriksnas J, Barone S, Witte D, Shull GE, Forte JG, Holm L, Soleimani M. SLC26A9 is expressed in gastric surface epithelial cells, mediates Cl-/HCO3- exchange, and is inhibited by NH4+. Am J Physiol Cell Physiol. 2005 Aug;289(2):C493-505. Epub 2005 Mar 30. PMID:15800055 doi:http://dx.doi.org/00030.2005
- ↑ Romero MF, Chang MH, Plata C, Zandi-Nejad K, Mercado A, Broumand V, Sussman CR, Mount DB. Physiology of electrogenic SLC26 paralogues. Novartis Found Symp. 2006;273:126-38; discussion 138-47, 261-4 PMID:17120765
- ↑ Walter JD, Sawicka M, Dutzler R. Cryo-EM structures and functional characterization of murine Slc26a9 reveal mechanism of uncoupled chloride transport. Elife. 2019 Jul 24;8. pii: 46986. doi: 10.7554/eLife.46986. PMID:31339488 doi:http://dx.doi.org/10.7554/eLife.46986
- ↑ Walter JD, Sawicka M, Dutzler R. Cryo-EM structures and functional characterization of murine Slc26a9 reveal mechanism of uncoupled chloride transport. Elife. 2019 Jul 24;8. pii: 46986. doi: 10.7554/eLife.46986. PMID:31339488 doi:http://dx.doi.org/10.7554/eLife.46986
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