View source for 8ijl


==Cyo-EM structure of wildtype non-gastric proton pump in the presence of Na+, AlF and ADP==
<StructureSection load='8ijl' size='340' side='right'caption='[[8ijl]], [[Resolution|resolution]] 2.62&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8ijl]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus Rattus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8IJL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8IJL 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]] 2.62&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=ALF:TETRAFLUOROALUMINATE+ION'>ALF</scene>, <scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PCW:1,2-DIOLEOYL-SN-GLYCERO-3-PHOSPHOCHOLINE'>PCW</scene>, <scene name='pdbligand=Q7G:2-{[(4-O-alpha-D-glucopyranosyl-alpha-D-glucopyranosyl)oxy]methyl}-4-{[(3beta,9beta,14beta,17beta,25R)-spirost-5-en-3-yl]oxy}butyl+4-O-alpha-D-glucopyranosyl-alpha-D-glucopyranoside'>Q7G</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=8ijl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8ijl OCA], [https://pdbe.org/8ijl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8ijl RCSB], [https://www.ebi.ac.uk/pdbsum/8ijl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8ijl ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/AT12A_RAT AT12A_RAT] The catalytic subunit of a H(+)/K(+) ATPase and/or Na(+)/K(+) ATPase pump which transports K(+) ions in exchange for Na(+) and/or H(+) ions across the apical membrane of epithelial cells. Uses ATP as an energy source to pump K(+) ions into the cell while transporting Na(+) and/or H(+) ions to the extracellular compartment (PubMed:10644526, PubMed:7560093). Involved in the maintenance of electrolyte homeostasis through K(+) ion absorption in kidney and colon (By similarity). In the airway epithelium, may play a primary role in mucus acidification regulating its viscosity and clearance (By similarity).[UniProtKB:P54707][UniProtKB:Q9Z1W8]<ref>PMID:10644526</ref> <ref>PMID:7560093</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The Na(+),K(+)-ATPase (NKA) and non-gastric H(+),K(+)- ATPase (ngHKA) share ~65 % sequence identity, and nearly identical catalytic cycles. These pumps alternate between inward-facing (E1) and outward-facing (E2) conformations and differ in their exported substrate (Na(+) or H(+)) and stoichiometries (3 Na(+):2 K(+) or 1 H(+):1 K(+)). We reported that structures of the NKA-mimetic ngHKA mutant K794S/A797P/W940/R949C (SPWC) with 2 K(+) occluded in E2-P(i) and 3 Na(+)-bound in E1.ATP states were nearly identical to NKA structures in equivalent states. Here we report the cryo-EM structures of K794A and K794S, two poorly-selective ngHKA mutants, under conditions to stabilize the E1.ATP state. Unexpectedly, the structures show a hybrid with both E1- and E2-like structural features. While transmembrane segments TM1-TM3 and TM4's extracellular half adopted an E2-like conformation, the rest of the protein assumed an E1 configuration. Two spherical densities, likely bound Na(+), were observed at cation-binding sites I and III, without density at site II. This explains the E2-like conformation of TM4's exoplasmic half. In NKA, oxygen atoms derived from the unwound portion of TM4 coordinated Na(+) at site II. Thus, the lack of Na(+) at site II of K794A/S prevents the luminal portion of TM4 from taking an E1-like position. The K794A structure also suggests that incomplete coordination of Na(+) at site III induces the halfway rotation of TM6, which impairs Na(+)-binding at the site II. Thus, our observations provide insight into the molecular mechanism of E2-E1 transition and cooperative Na(+)-binding in the NKA and other related cation pumps.

An unusual conformation from Na(+)-sensitive non-gastric proton pump mutants reveals molecular mechanisms of cooperative Na(+)-binding.,Abe K, Nishizawa T, Artigas P Biochim Biophys Acta Mol Cell Res. 2023 Oct;1870(7):119543. doi: , 10.1016/j.bbamcr.2023.119543. Epub 2023 Jul 22. PMID:37482134<ref>PMID:37482134</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8ijl" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Rattus]]
[[Category: Abe K]]