8ijm
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Cyo-EM structure of K794A non-gastric proton pump in Na+ bound E1AMPPCP state== | |
| + | <StructureSection load='8ijm' size='340' side='right'caption='[[8ijm]], [[Resolution|resolution]] 3.13Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8ijm]] 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=8IJM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8IJM 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]] 3.13Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACP:PHOSPHOMETHYLPHOSPHONIC+ACID+ADENYLATE+ESTER'>ACP</scene>, <scene name='pdbligand=CLR:CHOLESTEROL'>CLR</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></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=8ijm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8ijm OCA], [https://pdbe.org/8ijm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8ijm RCSB], [https://www.ebi.ac.uk/pdbsum/8ijm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8ijm 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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 8ijm" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Rattus]] | ||
| + | [[Category: Abe K]] | ||
Current revision
Cyo-EM structure of K794A non-gastric proton pump in Na+ bound E1AMPPCP state
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