View source for 8sie


==Pendrin in complex with bicarbonate==
<StructureSection load='8sie' size='340' side='right'caption='[[8sie]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8sie]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8SIE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8SIE 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]] 2.7&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AV0:(2~{R},3~{R},4~{S},5~{S},6~{R})-2-[(2~{R},3~{S},4~{R},5~{R},6~{R})-6-[2-decyl-2-[[(2~{R},3~{R},4~{R},5~{S},6~{R})-6-(hydroxymethyl)-5-[(2~{R},3~{R},4~{S},5~{S},6~{R})-6-(hydroxymethyl)-3,4,5-tris(oxidanyl)oxan-2-yl]oxy-3,4-bis(oxidanyl)oxan-2-yl]oxymethyl]dodecoxy]-2-(hydroxymethyl)-4,5-bis(oxidanyl)oxan-3-yl]oxy-6-(hydroxymethyl)oxane-3,4,5-triol'>AV0</scene>, <scene name='pdbligand=BCT:BICARBONATE+ION'>BCT</scene>, <scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=DMU:DECYL-BETA-D-MALTOPYRANOSIDE'>DMU</scene>, <scene name='pdbligand=LBN:[(2~{R})-3-hexadecanoyloxy-2-[(~{Z})-octadec-9-enoyl]oxy-propyl]+2-(trimethylazaniumyl)ethyl+phosphate'>LBN</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=8sie FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8sie OCA], [https://pdbe.org/8sie PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8sie RCSB], [https://www.ebi.ac.uk/pdbsum/8sie PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8sie ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/I3L8V6_PIG I3L8V6_PIG] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Pendrin (SLC26A4) is an anion exchanger that mediates bicarbonate (HCO(3)(-)) exchange for chloride (Cl(-)) and is crucial for maintaining pH and salt homeostasis in the kidney, lung, and cochlea. Pendrin also exports iodide (I(-)) in the thyroid gland. Pendrin mutations in humans lead to Pendred syndrome, causing hearing loss and goiter. Inhibition of pendrin is a validated approach for attenuating airway hyperresponsiveness in asthma and for treating hypertension. However, the mechanism of anion exchange and its inhibition by drugs remains poorly understood. We applied cryo-electron microscopy to determine structures of pendrin from Sus scrofa in the presence of either Cl(-), I(-), HCO(3)(-) or in the apo-state. The structures reveal two anion-binding sites in each protomer, and functional analyses show both sites are involved in anion exchange. The structures also show interactions between the Sulfate Transporter and Anti-Sigma factor antagonist (STAS) and transmembrane domains, and mutational studies suggest a regulatory role. We also determine the structure of pendrin in a complex with niflumic acid (NFA), which uncovers a mechanism of inhibition by competing with anion binding and impeding the structural changes necessary for anion exchange. These results reveal directions for understanding the mechanisms of anion selectivity and exchange and their regulations by the STAS domain. This work also establishes a foundation for analyzing the pathophysiology of mutations associated with Pendred syndrome.

Mechanism of anion exchange and small-molecule inhibition of pendrin.,Wang L, Hoang A, Gil-Iturbe E, Laganowsky A, Quick M, Zhou M Nat Commun. 2024 Jan 6;15(1):346. doi: 10.1038/s41467-023-44612-1. PMID:38184688<ref>PMID:38184688</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8sie" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Sus scrofa]]
[[Category: Hoang A]]
[[Category: Wang L]]
[[Category: Zhou M]]