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| ==CryoEM structure of human SLC4A4 sodium-coupled acid-base transporter NBCe1== | | ==CryoEM structure of human SLC4A4 sodium-coupled acid-base transporter NBCe1== |
| <StructureSection load='6caa' size='340' side='right' caption='[[6caa]], [[Resolution|resolution]] 3.90Å' scene=''> | | <SX load='6caa' size='340' side='right' viewer='molstar' caption='[[6caa]], [[Resolution|resolution]] 3.90Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[6caa]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CAA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CAA FirstGlance]. <br> | | <table><tr><td colspan='2'>[[6caa]] 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=6CAA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6CAA FirstGlance]. <br> |
| </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SLC4A4, NBC, NBC1, NBCE1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.9Å</td></tr> |
| <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6caa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6caa OCA], [http://pdbe.org/6caa PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6caa RCSB], [http://www.ebi.ac.uk/pdbsum/6caa PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6caa ProSAT]</span></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=6caa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6caa OCA], [https://pdbe.org/6caa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6caa RCSB], [https://www.ebi.ac.uk/pdbsum/6caa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6caa ProSAT]</span></td></tr> |
| </table> | | </table> |
| == Disease == | | == Disease == |
| [[http://www.uniprot.org/uniprot/S4A4_HUMAN S4A4_HUMAN]] Autosomal recessive proximal renal tubular acidosis. The disease is caused by mutations affecting the gene represented in this entry. Loss of interaction with and stimulation by CA4 is the cause of retinitis pigmentosa type 17 (RP17). | | [https://www.uniprot.org/uniprot/S4A4_HUMAN S4A4_HUMAN] Autosomal recessive proximal renal tubular acidosis. The disease is caused by mutations affecting the gene represented in this entry. Loss of interaction with and stimulation by CA4 is the cause of retinitis pigmentosa type 17 (RP17). |
| == Function == | | == Function == |
| [[http://www.uniprot.org/uniprot/S4A4_HUMAN S4A4_HUMAN]] Electrogenic sodium/bicarbonate cotransporter with a Na(+):HCO3(-) stoichiometry varying from 1:2 to 1:3. May regulate bicarbonate influx/efflux at the basolateral membrane of cells and regulate intracellular pH.<ref>PMID:10069984</ref> <ref>PMID:12907161</ref> <ref>PMID:16636648</ref> <ref>PMID:16769890</ref> <ref>PMID:17661077</ref> <ref>PMID:9235899</ref> <ref>PMID:9651366</ref> Isoform 2: May have a higher activity than isoform 1.<ref>PMID:16769890</ref> | | [https://www.uniprot.org/uniprot/S4A4_HUMAN S4A4_HUMAN] Electrogenic sodium/bicarbonate cotransporter with a Na(+):HCO3(-) stoichiometry varying from 1:2 to 1:3. May regulate bicarbonate influx/efflux at the basolateral membrane of cells and regulate intracellular pH.<ref>PMID:10069984</ref> <ref>PMID:12907161</ref> <ref>PMID:16636648</ref> <ref>PMID:16769890</ref> <ref>PMID:17661077</ref> <ref>PMID:9235899</ref> <ref>PMID:9651366</ref> Isoform 2: May have a higher activity than isoform 1.<ref>PMID:16769890</ref> |
| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| Na(+)-coupled acid-base transporters play essential roles in human biology. Their dysfunction has been linked to cancer, heart, and brain disease. High-resolution structures of mammalian Na(+)-coupled acid-base transporters are not available. The sodium-bicarbonate cotransporter NBCe1 functions in multiple organs and its mutations cause blindness, abnormal growth and blood chemistry, migraines, and impaired cognitive function. Here, we have determined the structure of the membrane domain dimer of human NBCe1 at 3.9 A resolution by cryo electron microscopy. Our atomic model and functional mutagenesis revealed the ion accessibility pathway and the ion coordination site, the latter containing residues involved in human disease-causing mutations. We identified a small number of residues within the ion coordination site whose modification transformed NBCe1 into an anion exchanger. Our data suggest that symporters and exchangers utilize comparable transport machinery and that subtle differences in their substrate-binding regions have very significant effects on their transport mode.
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| CryoEM structure of the human SLC4A4 sodium-coupled acid-base transporter NBCe1.,Huynh KW, Jiang J, Abuladze N, Tsirulnikov K, Kao L, Shao X, Newman D, Azimov R, Pushkin A, Zhou ZH, Kurtz I Nat Commun. 2018 Mar 2;9(1):900. doi: 10.1038/s41467-018-03271-3. PMID:29500354<ref>PMID:29500354</ref>
| | ==See Also== |
| | | *[[Symporter 3D structures|Symporter 3D structures]] |
| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 6caa" style="background-color:#fffaf0;"></div>
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| == References == | | == References == |
| <references/> | | <references/> |
| __TOC__ | | __TOC__ |
| </StructureSection> | | </SX> |
| [[Category: Human]] | | [[Category: Homo sapiens]] |
| [[Category: Abuladze, N]] | | [[Category: Large Structures]] |
| [[Category: Azimov, R]] | | [[Category: Abuladze N]] |
| [[Category: Huynh, K W]] | | [[Category: Azimov R]] |
| [[Category: Jiang, J]] | | [[Category: Huynh KW]] |
| [[Category: Kao, L]] | | [[Category: Jiang J]] |
| [[Category: Kurtz, I]] | | [[Category: Kao L]] |
| [[Category: Newman, D]] | | [[Category: Kurtz I]] |
| [[Category: Pushkin, A]] | | [[Category: Newman D]] |
| [[Category: Shao, X]] | | [[Category: Pushkin A]] |
| [[Category: Tsirulnikov, K]] | | [[Category: Shao X]] |
| [[Category: Zhou, Z H]] | | [[Category: Tsirulnikov K]] |
| [[Category: Electrogenic sodium-coupled bicarbonate cotransporter]]
| | [[Category: Zhou ZH]] |
| [[Category: Nbce1]]
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| [[Category: Slc4a4]]
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| [[Category: Transport protein]]
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