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| | ==Crystal structure of the regulatory domain of the sodium driven chloride bicarbonate exchanger.== | | ==Crystal structure of the regulatory domain of the sodium driven chloride bicarbonate exchanger.== |
| - | <StructureSection load='5jho' size='340' side='right' caption='[[5jho]], [[Resolution|resolution]] 2.80Å' scene=''> | + | <StructureSection load='5jho' size='340' side='right'caption='[[5jho]], [[Resolution|resolution]] 2.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5jho]] 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=5JHO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5JHO FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5jho]] 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=5JHO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5JHO FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SLC4A8, KIAA0739, NBC, NBC3, NDCBE1 ([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">X-ray diffraction, [[Resolution|Resolution]] 2.801Å</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=5jho FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jho OCA], [http://pdbe.org/5jho PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5jho RCSB], [http://www.ebi.ac.uk/pdbsum/5jho PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5jho 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=5jho FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jho OCA], [https://pdbe.org/5jho PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5jho RCSB], [https://www.ebi.ac.uk/pdbsum/5jho PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5jho ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/S4A8_HUMAN S4A8_HUMAN]] Mediates electroneutral sodium- and carbonate-dependent chloride-HCO3(-) exchange with a Na(+):HCO3(-) stoichiometry of 2:1. Plays a major role in pH regulation in neurons. May be involved in cell pH regulation by transporting HCO3(-) from blood to cell. Enhanced expression in severe acid stress could be important for cell survival by mediating the influx of HCO3(-) into the cells. Also mediates lithium-dependent HCO3(-) cotransport. May be regulated by osmolarity.<ref>PMID:10362779</ref> <ref>PMID:11133997</ref> | + | [https://www.uniprot.org/uniprot/S4A8_HUMAN S4A8_HUMAN] Mediates electroneutral sodium- and carbonate-dependent chloride-HCO3(-) exchange with a Na(+):HCO3(-) stoichiometry of 2:1. Plays a major role in pH regulation in neurons. May be involved in cell pH regulation by transporting HCO3(-) from blood to cell. Enhanced expression in severe acid stress could be important for cell survival by mediating the influx of HCO3(-) into the cells. Also mediates lithium-dependent HCO3(-) cotransport. May be regulated by osmolarity.<ref>PMID:10362779</ref> <ref>PMID:11133997</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Alvadia, C]] | + | [[Category: Large Structures]] |
| - | [[Category: Bjerregaard-Andersen, K]] | + | [[Category: Alvadia C]] |
| - | [[Category: Morth, J P]] | + | [[Category: Bjerregaard-Andersen K]] |
| - | [[Category: Sommer, T]] | + | [[Category: Morth JP]] |
| - | [[Category: Anion transport]]
| + | [[Category: Sommer T]] |
| - | [[Category: Bicarbonate exchanger]]
| + | |
| - | [[Category: Membrane protein]]
| + | |
| - | [[Category: Transport protein]]
| + | |
| Structural highlights
Function
S4A8_HUMAN Mediates electroneutral sodium- and carbonate-dependent chloride-HCO3(-) exchange with a Na(+):HCO3(-) stoichiometry of 2:1. Plays a major role in pH regulation in neurons. May be involved in cell pH regulation by transporting HCO3(-) from blood to cell. Enhanced expression in severe acid stress could be important for cell survival by mediating the influx of HCO3(-) into the cells. Also mediates lithium-dependent HCO3(-) cotransport. May be regulated by osmolarity.[1] [2]
Publication Abstract from PubMed
The sodium-driven chloride/bicarbonate exchanger (NDCBE) is essential for maintaining homeostatic pH in neurons. The crystal structure at 2.8 A resolution of the regulatory N-terminal domain of human NDCBE represents the first crystal structure of an electroneutral sodium-bicarbonate cotransporter. The crystal structure forms an equivalent dimeric interface as observed for the cytoplasmic domain of Band 3, and thus establishes that the consensus motif VTVLP is the key minimal dimerization motif. The VTVLP motif is highly conserved and likely to be the physiologically relevant interface for all other members of the SLC4 family. A novel conserved Zn2+-binding motif present in the N-terminal domain of NDCBE is identified and characterized in vitro. Cellular studies confirm the Zn2+ dependent transport of two electroneutral bicarbonate transporters, NCBE and NBCn1. The Zn2+ site is mapped to a cluster of histidines close to the conserved ETARWLKFEE motif and likely plays a role in the regulation of this important motif. The combined structural and bioinformatics analysis provides a model that predicts with additional confidence the physiologically relevant interface between the cytoplasmic domain and the transmembrane domain.
The crystal structure of the regulatory domain of the human sodium-driven chloride/bicarbonate exchanger.,Alvadia CM, Sommer T, Bjerregaard-Andersen K, Damkier HH, Montrasio M, Aalkjaer C, Morth JP Sci Rep. 2017 Sep 21;7(1):12131. doi: 10.1038/s41598-017-12409-0. PMID:28935959[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Amlal H, Burnham CE, Soleimani M. Characterization of Na+/HCO-3 cotransporter isoform NBC-3. Am J Physiol. 1999 Jun;276(6 Pt 2):F903-13. PMID:10362779
- ↑ Grichtchenko II, Choi I, Zhong X, Bray-Ward P, Russell JM, Boron WF. Cloning, characterization, and chromosomal mapping of a human electroneutral Na(+)-driven Cl-HCO3 exchanger. J Biol Chem. 2001 Mar 16;276(11):8358-63. Epub 2000 Dec 27. PMID:11133997 doi:http://dx.doi.org/10.1074/jbc.C000716200
- ↑ Alvadia CM, Sommer T, Bjerregaard-Andersen K, Damkier HH, Montrasio M, Aalkjaer C, Morth JP. The crystal structure of the regulatory domain of the human sodium-driven chloride/bicarbonate exchanger. Sci Rep. 2017 Sep 21;7(1):12131. doi: 10.1038/s41598-017-12409-0. PMID:28935959 doi:http://dx.doi.org/10.1038/s41598-017-12409-0
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