3gin

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of E454K-CBD1

Structural highlights

3gin is a 2 chain structure with sequence from Canis lupus familiaris. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.4Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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 mammalian Na(+)/Ca(2+) exchanger, NCX1.1, serves as the main mechanism for Ca(2+) efflux across the sarcolemma following cardiac contraction. In addition to transporting Ca(2+), NCX1.1 activity is also strongly regulated by Ca(2+) binding to two intracellular regulatory domains, CBD1 and CBD2. The structures of both of these domains have been solved by NMR spectroscopy and x-ray crystallography, greatly enhancing our understanding of Ca(2+) regulation. Nevertheless, the mechanisms by which Ca(2+) regulates the exchanger remain incompletely understood. The initial NMR study showed that the first regulatory domain, CBD1, unfolds in the absence of regulatory Ca(2+). It was further demonstrated that a mutation of an acidic residue involved in Ca(2+) binding, E454K, prevents this structural unfolding. A contradictory result was recently obtained in a second NMR study in which Ca(2+) removal merely triggered local rearrangements of CBD1. To address this issue, we solved the crystal structure of the E454K-CBD1 mutant and performed electrophysiological analyses of the full-length exchanger with mutations at position 454. We show that the lysine substitution replaces the Ca(2+) ion at position 1 of the CBD1 Ca(2+) binding site and participates in a charge compensation mechanism. Electrophysiological analyses show that mutations of residue Glu-454 have no impact on Ca(2+) regulation of NCX1.1. Together, structural and mutational analyses indicate that only two of the four Ca(2+) ions that bind to CBD1 are important for regulating exchanger activity.

Structure and functional analysis of a Ca2+ sensor mutant of the Na+/Ca2+ exchanger.,Chaptal V, Ottolia M, Mercado-Besserer G, Nicoll DA, Philipson KD, Abramson J J Biol Chem. 2009 May 29;284(22):14688-92. Epub 2009 Mar 30. PMID:19332552^[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
↑ 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

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3gin"

Categories: Canis lupus familiaris | Large Structures | Abramson J | Chaptal V | Mercado-Besserer G

@@ Line 1: / Line 1: @@
-[[Image:3gin.png|left|200px]]
-{{STRUCTURE_3gin|  PDB=3gin  |  SCENE=  }}
+==Crystal structure of E454K-CBD1==
+<StructureSection load='3gin' size='340' side='right'caption='[[3gin]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[3gin]] is a 2 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=3GIN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3GIN FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</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'>[https://proteopedia.org/fgij/fg.htm?mol=3gin FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gin OCA], [https://pdbe.org/3gin PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3gin RCSB], [https://www.ebi.ac.uk/pdbsum/3gin PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3gin ProSAT]</span></td></tr>
+</table>
+== 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 ==
+[[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/gi/3gin_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=3gin ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The mammalian Na(+)/Ca(2+) exchanger, NCX1.1, serves as the main mechanism for Ca(2+) efflux across the sarcolemma following cardiac contraction. In addition to transporting Ca(2+), NCX1.1 activity is also strongly regulated by Ca(2+) binding to two intracellular regulatory domains, CBD1 and CBD2. The structures of both of these domains have been solved by NMR spectroscopy and x-ray crystallography, greatly enhancing our understanding of Ca(2+) regulation. Nevertheless, the mechanisms by which Ca(2+) regulates the exchanger remain incompletely understood. The initial NMR study showed that the first regulatory domain, CBD1, unfolds in the absence of regulatory Ca(2+). It was further demonstrated that a mutation of an acidic residue involved in Ca(2+) binding, E454K, prevents this structural unfolding. A contradictory result was recently obtained in a second NMR study in which Ca(2+) removal merely triggered local rearrangements of CBD1. To address this issue, we solved the crystal structure of the E454K-CBD1 mutant and performed electrophysiological analyses of the full-length exchanger with mutations at position 454. We show that the lysine substitution replaces the Ca(2+) ion at position 1 of the CBD1 Ca(2+) binding site and participates in a charge compensation mechanism. Electrophysiological analyses show that mutations of residue Glu-454 have no impact on Ca(2+) regulation of NCX1.1. Together, structural and mutational analyses indicate that only two of the four Ca(2+) ions that bind to CBD1 are important for regulating exchanger activity.
-===Crystal structure of E454K-CBD1===
+Structure and functional analysis of a Ca2+ sensor mutant of the Na+/Ca2+ exchanger.,Chaptal V, Ottolia M, Mercado-Besserer G, Nicoll DA, Philipson KD, Abramson J J Biol Chem. 2009 May 29;284(22):14688-92. Epub 2009 Mar 30. PMID:19332552<ref>PMID:19332552</ref>
-{{ABSTRACT_PUBMED_19332552}}
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-==About this Structure==
+<div class="pdbe-citations 3gin" style="background-color:#fffaf0;"></div>
-[[3gin]] is a 2 chain structure with 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=3GIN OCA].
+== References ==
+<references/>
-==Reference==
+__TOC__
-<ref group="xtra">PMID:019332552</ref><references group="xtra"/>
+</StructureSection>
 [[Category: Canis lupus familiaris]]
-[[Category: Abramson, J.]]
+[[Category: Large Structures]]
-[[Category: Chaptal, V.]]
+[[Category: Abramson J]]
-[[Category: Mercado-Besserer, G.]]
+[[Category: Chaptal V]]
-[[Category: Antiport]]
+[[Category: Mercado-Besserer G]]
-[[Category: Calcium binding domain 1]]
-[[Category: Calcium transport]]
-[[Category: Calmodulin-binding]]
-[[Category: Cbd1]]
-[[Category: Cbd2]]
-[[Category: Cell membrane]]
-[[Category: Glycoprotein]]
-[[Category: Ion transport]]
-[[Category: Membrane]]
-[[Category: Metal binding protein]]
-[[Category: Metal transport]]
-[[Category: Ncx]]
-[[Category: Phosphoprotein]]
-[[Category: Sodium transport]]
-[[Category: Transmembrane]]
-[[Category: Transport]]

3gin

From Proteopedia

Current revision

Crystal structure of E454K-CBD1

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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