8opq

From Proteopedia

(Difference between revisions)

Current revision

Structure of Human Solute Carrier 26 family member A6 (SLC26A6) anion transporter in an inward-facing state

Structural highlights

8opq is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.28Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

S26A6_HUMAN Apical membrane anion-exchanger with wide epithelial distribution that plays a role as a component of the pH buffering system for maintaining acid-base homeostasis. Acts as a versatile DIDS-sensitive inorganic and organic anion transporter that mediates the uptake of monovalent anions like chloride, bicarbonate, formate and hydroxyl ion and divalent anions like sulfate and oxalate. Functions in multiple exchange modes involving pairs of these anions, which include chloride-bicarbonate, chloride-oxalate, oxalate-formate, oxalate-sulfate and chloride-formate exchange. Apical membrane chloride-bicarbonate exchanger that mediates luminal chloride absorption and bicarbonate secretion by the small intestinal brush border membrane and contributes to intracellular pH regulation in the duodenal upper villous epithelium during proton-coupled peptide absorption, possibly by providing a bicarbonate import pathway. Mediates also intestinal chloride absorption and oxalate secretion, thereby preventing hyperoxaluria and calcium oxalate urolithiasis. Transepithelial oxalate secretion, chloride-formate, chloride-oxalate and chloride-bicarbonate transport activities in the duodenum are inhibited by PKC activation in a calcium-independent manner. The apical membrane chloride-bicarbonate exchanger provides also a major route for fluid and bicarbonate secretion into the proximal tubules of the kidney as well as into the proximal part of the interlobular pancreatic ductal tree, where it mediates electrogenic chloride-bicarbonate exchange with a chloride-bicarbonate stoichiometry of 1:2, and hence will dilute and alkalinize protein-rich acinar secretion. Mediates also the transcellular sulfate absorption and oxalate secretion across the apical membrane in the duodenum and the formate ion efflux at the apical brush border of cells in the proximal tubules of kidney. Plays a role in sperm capacitation by increasing intracellular pH.[UniProtKB:Q8CIW6]^[1] ^[2] Apical membrane chloride-bicarbonate exchanger. Its association with carbonic anhydrase CA2 forms a bicarbonate transport metabolon; hence maximizes the local concentration of bicarbonate at the transporter site.^[3]

Publication Abstract from PubMed

Members of the SLC26 family constitute a conserved class of anion transport proteins, which encompasses uncoupled transporters with channel-like properties, coupled exchangers and motor proteins. Among the 10 functional paralogs in humans, several participate in the secretion of bicarbonate in exchange with chloride and thus play an important role in maintaining pH homeostasis. Previously, we have elucidated the structure of murine SLC26A9 and defined its function as an uncoupled chloride transporter (Walter et al., 2019). Here we have determined the structure of the closely related human transporter SLC26A6 and characterized it as a coupled exchanger of chloride with bicarbonate and presumably also oxalate. The structure defines an inward-facing conformation of the protein that generally resembles known structures of SLC26A9. The altered anion selectivity between both paralogs is a consequence of a remodeled ion binding site located in the center of a mobile unit of the membrane-inserted domain, which also accounts for differences in the coupling mechanism.

Structural and functional properties of the transporter SLC26A6 reveal mechanism of coupled anion exchange.,Tippett DN, Breen C, Butler SJ, Sawicka M, Dutzler R Elife. 2023 Jun 23;12:RP87178. doi: 10.7554/eLife.87178. PMID:37351578^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Freel RW, Morozumi M, Hatch M. Parsing apical oxalate exchange in Caco-2BBe1 monolayers: siRNA knockdown of SLC26A6 reveals the role and properties of PAT-1. Am J Physiol Gastrointest Liver Physiol. 2009 Nov;297(5):G918-29. PMID:20501439 doi:10.1152/ajpgi.00251.2009
↑ Thomson RB, Thomson CL, Aronson PS. N-glycosylation critically regulates function of oxalate transporter SLC26A6. Am J Physiol Cell Physiol. 2016 Dec 1;311(6):C866-C873. PMID:27681177 doi:10.1152/ajpcell.00171.2016
↑ Alvarez BV, Vilas GL, Casey JR. Metabolon disruption: a mechanism that regulates bicarbonate transport. EMBO J. 2005 Jul 20;24(14):2499-511. PMID:15990874 doi:10.1038/sj.emboj.7600736
↑ Tippett DN, Breen C, Butler SJ, Sawicka M, Dutzler R. Structural and functional properties of the transporter SLC26A6 reveal mechanism of coupled anion exchange. Elife. 2023 Jun 23;12:RP87178. PMID:37351578 doi:10.7554/eLife.87178

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/8opq"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 8opq is ON HOLD
+==Structure of Human Solute Carrier 26 family member A6 (SLC26A6) anion transporter in an inward-facing state==
+<StructureSection load='8opq' size='340' side='right'caption='[[8opq]], [[Resolution|resolution]] 3.28&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8opq]] 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=8OPQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8OPQ FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.28&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></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=8opq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8opq OCA], [https://pdbe.org/8opq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8opq RCSB], [https://www.ebi.ac.uk/pdbsum/8opq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8opq ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/S26A6_HUMAN S26A6_HUMAN] Apical membrane anion-exchanger with wide epithelial distribution that plays a role as a component of the pH buffering system for maintaining acid-base homeostasis. Acts as a versatile DIDS-sensitive inorganic and organic anion transporter that mediates the uptake of monovalent anions like chloride, bicarbonate, formate and hydroxyl ion and divalent anions like sulfate and oxalate. Functions in multiple exchange modes involving pairs of these anions, which include chloride-bicarbonate, chloride-oxalate, oxalate-formate, oxalate-sulfate and chloride-formate exchange. Apical membrane chloride-bicarbonate exchanger that mediates luminal chloride absorption and bicarbonate secretion by the small intestinal brush border membrane and contributes to intracellular pH regulation in the duodenal upper villous epithelium during proton-coupled peptide absorption, possibly by providing a bicarbonate import pathway. Mediates also intestinal chloride absorption and oxalate secretion, thereby preventing hyperoxaluria and calcium oxalate urolithiasis. Transepithelial oxalate secretion, chloride-formate, chloride-oxalate and chloride-bicarbonate transport activities in the duodenum are inhibited by PKC activation in a calcium-independent manner. The apical membrane chloride-bicarbonate exchanger provides also a major route for fluid and bicarbonate secretion into the proximal tubules of the kidney as well as into the proximal part of the interlobular pancreatic ductal tree, where it mediates electrogenic chloride-bicarbonate exchange with a chloride-bicarbonate stoichiometry of 1:2, and hence will dilute and alkalinize protein-rich acinar secretion. Mediates also the transcellular sulfate absorption and oxalate secretion across the apical membrane in the duodenum and the formate ion efflux at the apical brush border of cells in the proximal tubules of kidney. Plays a role in sperm capacitation by increasing intracellular pH.[UniProtKB:Q8CIW6]<ref>PMID:20501439</ref> <ref>PMID:27681177</ref>   Apical membrane chloride-bicarbonate exchanger. Its association with carbonic anhydrase CA2 forms a bicarbonate transport metabolon; hence maximizes the local concentration of bicarbonate at the transporter site.<ref>PMID:15990874</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Members of the SLC26 family constitute a conserved class of anion transport proteins, which encompasses uncoupled transporters with channel-like properties, coupled exchangers and motor proteins. Among the 10 functional paralogs in humans, several participate in the secretion of bicarbonate in exchange with chloride and thus play an important role in maintaining pH homeostasis. Previously, we have elucidated the structure of murine SLC26A9 and defined its function as an uncoupled chloride transporter (Walter et al., 2019). Here we have determined the structure of the closely related human transporter SLC26A6 and characterized it as a coupled exchanger of chloride with bicarbonate and presumably also oxalate. The structure defines an inward-facing conformation of the protein that generally resembles known structures of SLC26A9. The altered anion selectivity between both paralogs is a consequence of a remodeled ion binding site located in the center of a mobile unit of the membrane-inserted domain, which also accounts for differences in the coupling mechanism.
-Authors:
+Structural and functional properties of the transporter SLC26A6 reveal mechanism of coupled anion exchange.,Tippett DN, Breen C, Butler SJ, Sawicka M, Dutzler R Elife. 2023 Jun 23;12:RP87178. doi: 10.7554/eLife.87178. PMID:37351578<ref>PMID:37351578</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 8opq" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Virus coat proteins 3D structures|Virus coat proteins 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Breen C]]
+[[Category: Butler SJ]]
+[[Category: Dutzler R]]
+[[Category: Sawicka M]]
+[[Category: Tippett DN]]

8opq

From Proteopedia

Current revision

Structure of Human Solute Carrier 26 family member A6 (SLC26A6) anion transporter in an inward-facing state

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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