6y5v: Difference between revisions
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==Structure of Human Potassium Chloride Transporter KCC3b (S45D/T940D/T997D) in KCl== | ==Structure of Human Potassium Chloride Transporter KCC3b (S45D/T940D/T997D) in KCl== | ||
<StructureSection load='6y5v' size='340' side='right'caption='[[6y5v]]' scene=''> | <StructureSection load='6y5v' size='340' side='right'caption='[[6y5v]], [[Resolution|resolution]] 4.08Å' 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=6Y5V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6Y5V FirstGlance]. <br> | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6Y5V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6Y5V FirstGlance]. <br> | ||
</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=6y5v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6y5v OCA], [https://pdbe.org/6y5v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6y5v RCSB], [https://www.ebi.ac.uk/pdbsum/6y5v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6y5v ProSAT]</span></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]] 4.08Å</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=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=6y5v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6y5v OCA], [https://pdbe.org/6y5v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6y5v RCSB], [https://www.ebi.ac.uk/pdbsum/6y5v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6y5v ProSAT]</span></td></tr> | |||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Potassium-coupled chloride transporters (KCCs) play crucial roles in regulating cell volume and intracellular chloride concentration. They are characteristically inhibited under isotonic conditions via phospho-regulatory sites located within the cytoplasmic termini. Decreased inhibitory phosphorylation in response to hypotonic cell swelling stimulates transport activity, and dysfunction of this regulatory process has been associated with various human diseases. Here, we present cryo-EM structures of human KCC3b and KCC1, revealing structural determinants for phospho-regulation in both N- and C-termini. We show that phospho-mimetic KCC3b is arrested in an inward-facing state in which intracellular ion access is blocked by extensive contacts with the N-terminus. In another mutant with increased isotonic transport activity, KCC1Delta19, this interdomain interaction is absent, likely due to a unique phospho-regulatory site in the KCC1 N-terminus. Furthermore, we map additional phosphorylation sites as well as a previously unknown ATP/ADP-binding pocket in the large C-terminal domain and show enhanced thermal stabilization of other CCCs by adenine nucleotides. These findings provide fundamentally new insights into the complex regulation of KCCs and may unlock innovative strategies for drug development. | |||
Phospho-regulation, nucleotide binding and ion access control in potassium-chloride cotransporters.,Chi G, Ebenhoch R, Man H, Tang H, Tremblay LE, Reggiano G, Qiu X, Bohstedt T, Liko I, Almeida FG, Garneau AP, Wang D, McKinley G, Moreau CP, Bountra KD, Abrusci P, Mukhopadhyay SMM, Fernandez-Cid A, Slimani S, Lavoie JL, Burgess-Brown NA, Tehan B, DiMaio F, Jazayeri A, Isenring P, Robinson CV, Durr KL EMBO J. 2021 May 25:e107294. doi: 10.15252/embj.2020107294. PMID:34031912<ref>PMID:34031912</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6y5v" 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 08:29, 17 October 2024
Structure of Human Potassium Chloride Transporter KCC3b (S45D/T940D/T997D) in KCl
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