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[[Image:2dpk.gif|left|200px]]


{{Structure
==The Crystal Structure of the Primary Ca2+ Sensor of the Na+/Ca2+ Exchanger==
|PDB= 2dpk |SIZE=350|CAPTION= <scene name='initialview01'>2dpk</scene>, resolution 2.50&Aring;
<StructureSection load='2dpk' size='340' side='right'caption='[[2dpk]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
|SITE=  
== Structural highlights ==
|LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GAI:GUANIDINE'>GAI</scene> and <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID'>EPE</scene>
<table><tr><td colspan='2'>[[2dpk]] 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=2DPK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2DPK FirstGlance]. <br>
|ACTIVITY=  
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5&#8491;</td></tr>
|GENE=  
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=GAI:GUANIDINE'>GAI</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=2dpk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2dpk OCA], [https://pdbe.org/2dpk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2dpk RCSB], [https://www.ebi.ac.uk/pdbsum/2dpk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2dpk ProSAT]</span></td></tr>
 
</table>
'''The Crystal Structure of the Primary Ca2+ Sensor of the Na+/Ca2+ Exchanger'''
== Function ==
 
[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 ==
==Overview==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/dp/2dpk_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2dpk ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The Na+/Ca2+ exchanger is a plasma membrane protein that regulates intracellular Ca2+ levels in cardiac myocytes. Transport activity is governed by Ca2+, and the primary Ca2+ sensor (CBD1) is located in a large cytoplasmic loop connecting two transmembrane helices. The binding of Ca2+ to the CBD1 sensory domain results in conformational changes that stimulate the exchanger to extrude Ca2+. Here, we present a crystal structure of CBD1 at 2.5A resolution, which reveals a novel Ca2+ binding site consisting of four Ca2+ ions arranged in a tight planar cluster. This intricate coordination pattern for a Ca2+ binding cluster is indicative of a highly sensitive Ca2+ sensor and may represent a general platform for Ca2+ sensing.
The Na+/Ca2+ exchanger is a plasma membrane protein that regulates intracellular Ca2+ levels in cardiac myocytes. Transport activity is governed by Ca2+, and the primary Ca2+ sensor (CBD1) is located in a large cytoplasmic loop connecting two transmembrane helices. The binding of Ca2+ to the CBD1 sensory domain results in conformational changes that stimulate the exchanger to extrude Ca2+. Here, we present a crystal structure of CBD1 at 2.5A resolution, which reveals a novel Ca2+ binding site consisting of four Ca2+ ions arranged in a tight planar cluster. This intricate coordination pattern for a Ca2+ binding cluster is indicative of a highly sensitive Ca2+ sensor and may represent a general platform for Ca2+ sensing.


==About this Structure==
The crystal structure of the primary Ca2+ sensor of the Na+/Ca2+ exchanger reveals a novel Ca2+ binding motif.,Nicoll DA, Sawaya MR, Kwon S, Cascio D, Philipson KD, Abramson J J Biol Chem. 2006 Aug 4;281(31):21577-81. Epub 2006 Jun 14. PMID:16774926<ref>PMID:16774926</ref>
2DPK is a [[Single protein]] structure of sequence from [http://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=2DPK OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
The crystal structure of the primary Ca2+ sensor of the Na+/Ca2+ exchanger reveals a novel Ca2+ binding motif., Nicoll DA, Sawaya MR, Kwon S, Cascio D, Philipson KD, Abramson J, J Biol Chem. 2006 Aug 4;281(31):21577-81. Epub 2006 Jun 14. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16774926 16774926]
</div>
<div class="pdbe-citations 2dpk" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Canis lupus familiaris]]
[[Category: Canis lupus familiaris]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Abramson, J.]]
[[Category: Abramson J]]
[[Category: Sawaya, M.]]
[[Category: Sawaya M]]
[[Category: CA]]
[[Category: EPE]]
[[Category: GAI]]
[[Category: beta-bulge]]
[[Category: beta-sandwich]]
[[Category: calcium sensory domain]]
[[Category: cis-proline]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 16:29:52 2008''

Latest revision as of 07:51, 23 October 2024

The Crystal Structure of the Primary Ca2+ Sensor of the Na+/Ca2+ Exchanger

2dpk, resolution 2.50Å

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