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| | ==First Ca2+ binding domain of the Na,Ca-exchanger (NCX1)== | | ==First Ca2+ binding domain of the Na,Ca-exchanger (NCX1)== |
| - | <StructureSection load='2fws' size='340' side='right' caption='[[2fws]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2fws' size='340' side='right'caption='[[2fws]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2fws]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Canlf Canlf]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FWS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2FWS FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2fws]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Canis_lupus_familiaris Canis lupus familiaris]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FWS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2FWS FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2fwu|2fwu]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NCX1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9615 CANLF])</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=2fws FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fws OCA], [https://pdbe.org/2fws PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2fws RCSB], [https://www.ebi.ac.uk/pdbsum/2fws PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2fws ProSAT]</span></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=2fws FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fws OCA], [http://pdbe.org/2fws PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2fws RCSB], [http://www.ebi.ac.uk/pdbsum/2fws PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2fws ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/NAC1_CANFA NAC1_CANFA]] Rapidly transports Ca(2+) during excitation-contraction coupling. Ca(2+) is extruded from the cell during relaxation so as to prevent overloading of intracellular stores. | + | [https://www.uniprot.org/uniprot/NAC1_CANLF NAC1_CANLF] Mediates the exchange of one Ca(2+) ion against three to four Na(+) ions across the cell membrane, and thereby contributes to the regulation of cytoplasmic Ca(2+) levels and Ca(2+)-dependent cellular processes (PubMed:1700476, PubMed:1785844, PubMed:9486131, PubMed:17962412). Contributes to Ca(2+) transport during excitation-contraction coupling in muscle. In a first phase, voltage-gated channels mediate the rapid increase of cytoplasmic Ca(2+) levels due to release of Ca(2+) stores from the endoplasmic reticulum. SLC8A1 mediates the export of Ca(2+) from the cell during the next phase, so that cytoplasmic Ca(2+) levels rapidly return to baseline. Required for normal embryonic heart development and the onset of heart contractions (By similarity).[UniProtKB:P70414]<ref>PMID:1700476</ref> <ref>PMID:1785844</ref> <ref>PMID:17962412</ref> <ref>PMID:19332552</ref> <ref>PMID:9486131</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Canlf]] | + | [[Category: Canis lupus familiaris]] |
| - | [[Category: Aelen, J]] | + | [[Category: Large Structures]] |
| - | [[Category: Hilge, M]] | + | [[Category: Aelen J]] |
| - | [[Category: Vuister, G W]] | + | [[Category: Hilge M]] |
| - | [[Category: Beta-bulge]] | + | [[Category: Vuister GW]] |
| - | [[Category: Beta-sandwich]]
| + | |
| - | [[Category: Ca2+ binding]]
| + | |
| - | [[Category: Cis-proline]]
| + | |
| - | [[Category: Greek key]]
| + | |
| - | [[Category: Metal transport regulator]]
| + | |
| Structural highlights
Function
NAC1_CANLF Mediates the exchange of one Ca(2+) ion against three to four Na(+) ions across the cell membrane, and thereby contributes to the regulation of cytoplasmic Ca(2+) levels and Ca(2+)-dependent cellular processes (PubMed:1700476, PubMed:1785844, PubMed:9486131, PubMed:17962412). Contributes to Ca(2+) transport during excitation-contraction coupling in muscle. In a first phase, voltage-gated channels mediate the rapid increase of cytoplasmic Ca(2+) levels due to release of Ca(2+) stores from the endoplasmic reticulum. SLC8A1 mediates the export of Ca(2+) from the cell during the next phase, so that cytoplasmic Ca(2+) levels rapidly return to baseline. Required for normal embryonic heart development and the onset of heart contractions (By similarity).[UniProtKB:P70414][1] [2] [3] [4] [5]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The plasma membrane Na+/Ca2+ exchanger (NCX) is almost certainly the major Ca2+ extrusion mechanism in cardiac myocytes. Binding of Na+ and Ca2+ ions to its large cytosolic loop regulates ion transport of the exchanger. We determined the solution structures of two Ca2+ binding domains (CBD1 and CBD2) that, together with an alpha-catenin-like domain (CLD), form the regulatory exchanger loop. CBD1 and CBD2 are very similar in the Ca2+ bound state and describe the Calx-beta motif. Strikingly, in the absence of Ca2+, the upper half of CBD1 unfolds while CBD2 maintains its structural integrity. Together with a 7-fold higher affinity for Ca2+, this suggests that CBD1 is the primary Ca2+ sensor. Specific point mutations in either domain largely allow the interchange of their functionality and uncover the mechanism underlying Ca2+ sensing in NCX.
Ca2+ regulation in the Na+/Ca2+ exchanger involves two markedly different Ca2+ sensors.,Hilge M, Aelen J, Vuister GW Mol Cell. 2006 Apr 7;22(1):15-25. PMID:16600866[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Nicoll DA, Longoni S, Philipson KD. Molecular cloning and functional expression of the cardiac sarcolemmal Na(+)-Ca2+ exchanger. Science. 1990 Oct 26;250(4980):562-5. PMID:1700476
- ↑ Nicoll DA, Philipson KD. Molecular studies of the cardiac sarcolemmal sodium-calcium exchanger. Ann N Y Acad Sci. 1991;639:181-8. PMID:1785844
- ↑ Besserer GM, Ottolia M, Nicoll DA, Chaptal V, Cascio D, Philipson KD, Abramson J. The second Ca2+-binding domain of the Na+ Ca2+ exchanger is essential for regulation: crystal structures and mutational analysis. Proc Natl Acad Sci U S A. 2007 Nov 20;104(47):18467-72. Epub 2007 Oct 25. PMID:17962412
- ↑ Chaptal V, Ottolia M, Mercado-Besserer G, Nicoll DA, Philipson KD, Abramson J. Structure and functional analysis of a Ca2+ sensor mutant of the Na+/Ca2+ exchanger. J Biol Chem. 2009 May 29;284(22):14688-92. Epub 2009 Mar 30. PMID:19332552 doi:10.1074/jbc.C900037200
- ↑ Linck B, Qiu Z, He Z, Tong Q, Hilgemann DW, Philipson KD. Functional comparison of the three isoforms of the Na+/Ca2+ exchanger (NCX1, NCX2, NCX3). Am J Physiol. 1998 Feb;274(2 Pt 1):C415-23. PMID:9486131
- ↑ Hilge M, Aelen J, Vuister GW. Ca2+ regulation in the Na+/Ca2+ exchanger involves two markedly different Ca2+ sensors. Mol Cell. 2006 Apr 7;22(1):15-25. PMID:16600866 doi:10.1016/j.molcel.2006.03.008
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