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| | <StructureSection load='3us9' size='340' side='right'caption='[[3us9]], [[Resolution|resolution]] 2.68Å' scene=''> | | <StructureSection load='3us9' size='340' side='right'caption='[[3us9]], [[Resolution|resolution]] 2.68Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3us9]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Canlf Canlf]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3US9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3US9 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3us9]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Canis_lupus_familiaris Canis lupus familiaris]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3US9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3US9 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">X-ray diffraction, [[Resolution|Resolution]] 2.68Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SLC8A1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9615 CANLF])</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='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=3us9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3us9 OCA], [http://pdbe.org/3us9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3us9 RCSB], [http://www.ebi.ac.uk/pdbsum/3us9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3us9 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=3us9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3us9 OCA], [https://pdbe.org/3us9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3us9 RCSB], [https://www.ebi.ac.uk/pdbsum/3us9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3us9 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> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 3us9" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 3us9" style="background-color:#fffaf0;"></div> |
| - | | |
| - | ==See Also== | |
| - | *[[Sodium-calcium exchanger|Sodium-calcium exchanger]] | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Canlf]] | + | [[Category: Canis lupus familiaris]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Giladi, M]] | + | [[Category: Giladi M]] |
| - | [[Category: Hirsch, J A]] | + | [[Category: Hirsch JA]] |
| - | [[Category: Khananshvili, D]] | + | [[Category: Khananshvili D]] |
| - | [[Category: Sasson, Y]] | + | [[Category: Sasson Y]] |
| - | [[Category: Beta-sandwich]]
| + | |
| - | [[Category: Calcium binding protein]]
| + | |
| - | [[Category: Intracellular]]
| + | |
| - | [[Category: Metal binding protein]]
| + | |
| 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]
Publication Abstract from PubMed
Na(+)/Ca(2+) exchanger (NCX) proteins mediate Ca(2+)-fluxes across the cell membrane to maintain Ca(2+) homeostasis in many cell types. Eukaryotic NCX contains Ca(2+)-binding regulatory domains, CBD1 and CBD2. Ca(2+) binding to a primary sensor (Ca3-Ca4 sites) on CBD1 activates mammalian NCXs, whereas CALX, a Drosophila NCX ortholog, displays an inhibitory response to regulatory Ca(2+). To further elucidate the underlying regulatory mechanisms, we determined the 2.7 A crystal structure of mammalian CBD12-E454K, a two-domain construct that retains wild-type properties. In conjunction with stopped-flow kinetics and SAXS (small-angle X-ray scattering) analyses of CBD12 mutants, we show that Ca(2+) binding to Ca3-Ca4 sites tethers the domains via a network of interdomain salt-bridges. This Ca(2+)-driven interdomain switch controls slow dissociation of "occluded" Ca(2+) from the primary sensor and thus dictates Ca(2+) sensing dynamics. In the Ca(2+)-bound conformation, the interdomain angle of CBD12 is very similar in NCX and CALX, meaning that the interdomain distances cannot account for regulatory diversity in NCX and CALX. Since the two-domain interface is nearly identical among eukaryotic NCXs, including CALX, we suggest that the Ca(2+)-driven interdomain switch described here represents a general mechanism for initial conduction of regulatory signals in NCX variants.
A common Ca2+-driven interdomain module governs eukaryotic NCX regulation.,Giladi M, Sasson Y, Fang X, Hiller R, Buki T, Wang YX, Hirsch JA, Khananshvili D PLoS One. 2012;7(6):e39985. doi: 10.1371/journal.pone.0039985. Epub 2012 Jun 29. PMID:22768191[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
- ↑ Giladi M, Sasson Y, Fang X, Hiller R, Buki T, Wang YX, Hirsch JA, Khananshvili D. A common Ca2+-driven interdomain module governs eukaryotic NCX regulation. PLoS One. 2012;7(6):e39985. doi: 10.1371/journal.pone.0039985. Epub 2012 Jun 29. PMID:22768191 doi:http://dx.doi.org/10.1371/journal.pone.0039985
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