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==Cryo-EM structure of the potassium-chloride cotransporter KCC4 in lipid nanodiscs== | ==Cryo-EM structure of the potassium-chloride cotransporter KCC4 in lipid nanodiscs== | ||
<StructureSection load='6ukn' size='340' side='right'caption='[[6ukn]]' scene=''> | <StructureSection load='6ukn' size='340' side='right'caption='[[6ukn]], [[Resolution|resolution]] 3.65Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UKN OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UKN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6UKN FirstGlance]. <br> | ||
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.65Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=6ukn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ukn OCA], [https://pdbe.org/6ukn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ukn RCSB], [https://www.ebi.ac.uk/pdbsum/6ukn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ukn ProSAT]</span></td></tr> | |||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Cation-chloride-cotransporters (CCCs) catalyze transport of Cl(-) with K(+) and/or Na(+)across cellular membranes. CCCs play roles in cellular volume regulation, neural development and function, audition, regulation of blood pressure, and renal function. CCCs are targets of clinically important drugs including loop diuretics and their disruption has been implicated in pathophysiology including epilepsy, hearing loss, and the genetic disorders Andermann, Gitelman, and Bartter syndromes. Here we present the structure of a CCC, the Mus musculus K(+)-Cl(-) cotransporter (KCC) KCC4, in lipid nanodiscs determined by cryo-EM. The structure, captured in an inside-open conformation, reveals the architecture of KCCs including an extracellular domain poised to regulate transport activity through an outer gate. We identify binding sites for substrate K(+) and Cl(-) ions, demonstrate the importance of key coordinating residues for transporter activity, and provide a structural explanation for varied substrate specificity and ion transport ratio among CCCs. These results provide mechanistic insight into the function and regulation of a physiologically important transporter family. | |||
Cryo-EM structure of the potassium-chloride cotransporter KCC4 in lipid nanodiscs.,Reid MS, Kern DM, Brohawn SG Elife. 2020 Apr 14;9. pii: 52505. doi: 10.7554/eLife.52505. PMID:32286222<ref>PMID:32286222</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6ukn" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Solute carrier family 12 3D structures|Solute carrier family 12 3D structures]] | |||
*[[Symporter 3D structures|Symporter 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Latest revision as of 10:33, 23 October 2024
Cryo-EM structure of the potassium-chloride cotransporter KCC4 in lipid nanodiscs
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