View source for 7tti


==Human KCC1 bound with VU0463271 In an outward-open state==
<StructureSection load='7tti' size='340' side='right'caption='[[7tti]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7tti]] 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=7TTI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TTI 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]] 3.5&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=JUX:~{N}-cyclopropyl-~{N}-(4-methyl-1,3-thiazol-2-yl)-2-(6-phenylpyridazin-3-yl)sulfanyl-ethanamide'>JUX</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=7tti FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7tti OCA], [https://pdbe.org/7tti PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7tti RCSB], [https://www.ebi.ac.uk/pdbsum/7tti PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7tti ProSAT]</span></td></tr>
</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.
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== Publication Abstract from PubMed ==
Cation-chloride cotransporters (CCCs) catalyze electroneutral symport of Cl(-) with Na(+) and/or K(+) across membranes. CCCs are fundamental in cell volume homeostasis, transepithelia ion movement, maintenance of intracellular Cl(-) concentration, and neuronal excitability. Here, we present a cryoelectron microscopy structure of human K(+)-Cl(-) cotransporter (KCC)1 bound with the VU0463271 inhibitor in an outward-open state. In contrast to many other amino acid-polyamine-organocation transporter cousins, our first outward-open CCC structure reveals that opening the KCC1 extracellular ion permeation path does not involve hinge-bending motions of the transmembrane (TM) 1 and TM6 half-helices. Instead, rocking of TM3 and TM8, together with displacements of TM4, TM9, and a conserved intracellular loop 1 helix, underlie alternate opening and closing of extracellular and cytoplasmic vestibules. We show that KCC1 intriguingly exists in one of two distinct dimeric states via different intersubunit interfaces. Our studies provide a blueprint for understanding the mechanisms of CCCs and their inhibition by small molecule compounds.

Structure of the human cation-chloride cotransport KCC1 in an outward-open state.,Zhao Y, Shen J, Wang Q, Ruiz Munevar MJ, Vidossich P, De Vivo M, Zhou M, Cao E Proc Natl Acad Sci U S A. 2022 Jul 5;119(27):e2109083119. doi: , 10.1073/pnas.2109083119. Epub 2022 Jun 27. PMID:35759661<ref>PMID:35759661</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 7tti" style="background-color:#fffaf0;"></div>

==See Also==
*[[Solute carrier family 12 3D structures|Solute carrier family 12 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Cao EH]]
[[Category: Zhao YX]]