View source for 7zgo


==Cryo-EM structure of human NKCC1 (TM domain)==
<StructureSection load='7zgo' size='340' side='right'caption='[[7zgo]], [[Resolution|resolution]] 2.55&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7zgo]] 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=7ZGO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ZGO 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]] 2.55&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=POV:(2S)-3-(HEXADECANOYLOXY)-2-[(9Z)-OCTADEC-9-ENOYLOXY]PROPYL+2-(TRIMETHYLAMMONIO)ETHYL+PHOSPHATE'>POV</scene>, <scene name='pdbligand=Y01:CHOLESTEROL+HEMISUCCINATE'>Y01</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=7zgo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7zgo OCA], [https://pdbe.org/7zgo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7zgo RCSB], [https://www.ebi.ac.uk/pdbsum/7zgo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7zgo ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/S12A2_HUMAN S12A2_HUMAN] Electrically silent transporter system. Mediates sodium and chloride reabsorption. Plays a vital role in the regulation of ionic balance and cell volume.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The sodium-potassium-chloride transporter NKCC1 of the SLC12 family performs Na(+) -dependent Cl(-) - and K(+) -ion uptake across plasma membranes. NKCC1 is important for regulating cell volume, hearing, blood pressure, and regulation of hyperpolarizing GABAergic and glycinergic signaling in the central nervous system. Here, we present a 2.6 A resolution cryo-electron microscopy structure of human NKCC1 in the substrate-loaded (Na(+) , K(+) , and 2 Cl(-) ) and occluded, inward-facing state that has also been observed for the SLC6-type transporters MhsT and LeuT. Cl(-) binding at the Cl1 site together with the nearby K(+) ion provides a crucial bridge between the LeuT-fold scaffold and bundle domains. Cl(-) -ion binding at the Cl2 site seems to undertake a structural role similar to conserved glutamate of SLC6 transporters and may allow for Cl(-) -sensitive regulation of transport. Supported by functional studies in mammalian cells and computational simulations, we describe a putative Na(+) release pathway along transmembrane helix 5 coupled to the Cl2 site. The results provide insight into the structure-function relationship of NKCC1 with broader implications for other SLC12 family members.

Cryo-EM structure of the human NKCC1 transporter reveals mechanisms of ion coupling and specificity.,Neumann C, Rosenbaek LL, Flygaard RK, Habeck M, Karlsen JL, Wang Y, Lindorff-Larsen K, Gad HH, Hartmann R, Lyons JA, Fenton RA, Nissen P EMBO J. 2022 Dec 1;41(23):e110169. doi: 10.15252/embj.2021110169. Epub 2022 Oct , 14. PMID:36239040<ref>PMID:36239040</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7zgo" 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__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Fenton R]]
[[Category: Gad H]]
[[Category: Habeck M]]
[[Category: Hartmann R]]
[[Category: Kock Flygaard R]]
[[Category: Lindorff-Larsen K]]
[[Category: Lindtoft Rosenbaek L]]
[[Category: Lykkegaard Karlsen J]]
[[Category: Lyons J]]
[[Category: Neumann C]]
[[Category: Nissen P]]
[[Category: Wang Y]]