8wa5: Difference between revisions
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==Cryo-EM structure of the gastric proton pump Y799W/E936Q mutant in K+-occluded (K+)E2-AlF state== | |||
<StructureSection load='8wa5' size='340' side='right'caption='[[8wa5]], [[Resolution|resolution]] 2.51Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8wa5]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8WA5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8WA5 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]] 2.51Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ALF:TETRAFLUOROALUMINATE+ION'>ALF</scene>, <scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=8wa5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8wa5 OCA], [https://pdbe.org/8wa5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8wa5 RCSB], [https://www.ebi.ac.uk/pdbsum/8wa5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8wa5 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/ATP4A_PIG ATP4A_PIG] Catalyzes the hydrolysis of ATP coupled with the exchange of H(+) and K(+) ions across the plasma membrane. Responsible for acid production in the stomach. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The gastric proton pump (H(+),K(+)-ATPase) transports a proton into the stomach lumen for every K(+) ion exchanged in the opposite direction. In the lumen-facing state of the pump (E2), the pump selectively binds K(+) despite the presence of a 10-fold higher concentration of Na(+). The molecular basis for the ion selectivity of the pump is unknown. Using molecular dynamics simulations, free energy calculations, and Na(+) and K(+)-dependent ATPase activity assays, we demonstrate that the K(+) selectivity of the pump depends upon the simultaneous protonation of the acidic residues E343 and E795 in the ion-binding site. We also show that when E936 is protonated, the pump becomes Na(+) sensitive. The protonation-mimetic mutant E936Q exhibits weak Na(+)-activated ATPase activity. A 2.5-A resolution cryo-EM structure of the E936Q mutant in the K(+)-occluded E2-Pi form shows, however, no significant structural difference compared with wildtype except less-than-ideal coordination of K(+) in the mutant. The selectivity toward a specific ion correlates with a more rigid and less fluctuating ion-binding site. Despite being exposed to a pH of 1, the fundamental principle driving the K(+) ion selectivity of H(+),K(+)-ATPase is similar to that of Na(+),K(+)-ATPase: the ionization states of the acidic residues in the ion-binding sites determine ion selectivity. Unlike the Na(+),K(+)-ATPase, however, protonation of an ion-binding glutamate residue (E936) confers Na(+) sensitivity. | |||
Specific protonation of acidic residues confers K(+) selectivity to the gastric proton pump.,Madapally HV, Abe K, Dubey V, Khandelia H J Biol Chem. 2024 Jan;300(1):105542. doi: 10.1016/j.jbc.2023.105542. Epub 2023 , Dec 10. PMID:38072058<ref>PMID:38072058</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 8wa5" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Sus scrofa]] | |||
[[Category: Abe K]] | |||