7aip: Difference between revisions
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==Structure of Human Potassium Chloride Transporter KCC1 in NaCl (Reference Map)== | ==Structure of Human Potassium Chloride Transporter KCC1 in NaCl (Reference Map)== | ||
<StructureSection load='7aip' size='340' side='right'caption='[[7aip]]' scene=''> | <StructureSection load='7aip' size='340' side='right'caption='[[7aip]], [[Resolution|resolution]] 3.12Å' 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=7AIP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AIP FirstGlance]. <br> | <table><tr><td colspan='2'>[[7aip]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AIP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AIP 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=7aip FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7aip OCA], [https://pdbe.org/7aip PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7aip RCSB], [https://www.ebi.ac.uk/pdbsum/7aip PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7aip ProSAT]</span></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | ||
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[7ain|7ain]], [[7aio|7aio]]</div></td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SLC12A4, KCC1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=7aip FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7aip OCA], [https://pdbe.org/7aip PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7aip RCSB], [https://www.ebi.ac.uk/pdbsum/7aip PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7aip ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[[https://www.uniprot.org/uniprot/S12A4_HUMAN S12A4_HUMAN]] Mediates electroneutral potassium-chloride cotransport when activated by cell swelling. May contribute to cell volume homeostasis in single cells. May be involved in the regulation of basolateral Cl(-) exit in NaCl absorbing epithelia (By similarity). Isoform 4 has no transport activity. | |||
<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 7aip" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Human]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Abrusci P]] | [[Category: Abrusci, P]] | ||
[[Category: Almeida | [[Category: Almeida, F G]] | ||
[[Category: Arrowsmith | [[Category: Arrowsmith, C H]] | ||
[[Category: Bohstedt T]] | [[Category: Bohstedt, T]] | ||
[[Category: Bountra C]] | [[Category: Bountra, C]] | ||
[[Category: Burgess-Brown | [[Category: Burgess-Brown, N A]] | ||
[[Category: Chalk R]] | [[Category: Chalk, R]] | ||
[[Category: Chi G]] | [[Category: Chi, G]] | ||
[[Category: Duerr | [[Category: Duerr, K L]] | ||
[[Category: Ebenhoch R]] | [[Category: Ebenhoch, R]] | ||
[[Category: Edwards | [[Category: Edwards, A M]] | ||
[[Category: Elkins J]] | [[Category: Elkins, J]] | ||
[[Category: Liko I]] | [[Category: Liko, I]] | ||
[[Category: MacLean | [[Category: MacLean, E M]] | ||
[[Category: Man H]] | [[Category: Man, H]] | ||
[[Category: Marsden | [[Category: Marsden, B D]] | ||
[[Category: McKinley G]] | [[Category: McKinley, G]] | ||
[[Category: Moreau C]] | [[Category: Moreau, C]] | ||
[[Category: Mukhopadhyay | [[Category: Mukhopadhyay, S M.M]] | ||
[[Category: Robinson | [[Category: Robinson, C V]] | ||
[[Category: Singh | [[Category: Structural genomic]] | ||
[[Category: Snee M]] | [[Category: Singh, N K]] | ||
[[Category: Tang H]] | [[Category: Snee, M]] | ||
[[Category: Tehan | [[Category: Tang, H]] | ||
[[Category: Wang D]] | [[Category: Tehan, B G]] | ||
[[Category: Wang, D]] | |||
[[Category: Ccc]] | |||
[[Category: Homodimer]] | |||
[[Category: Human membrane protein]] | |||
[[Category: Kcc]] | |||
[[Category: Kcc1]] | |||
[[Category: Nucleotide-binding]] | |||
[[Category: Potassium-chloride coupled transporter]] | |||
[[Category: Sgc]] | |||
[[Category: Transport protein]] | |||
[[Category: Transporter]] | |||