2fwu

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(New page: 200px<br /><applet load="2fwu" size="450" color="white" frame="true" align="right" spinBox="true" caption="2fwu" /> '''Second Ca2+ binding domain of the Na,Ca-exch...)
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[[Image:2fwu.gif|left|200px]]<br /><applet load="2fwu" size="450" color="white" frame="true" align="right" spinBox="true"
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[[Image:2fwu.gif|left|200px]]<br /><applet load="2fwu" size="350" color="white" frame="true" align="right" spinBox="true"
caption="2fwu" />
caption="2fwu" />
'''Second Ca2+ binding domain of the Na,Ca-exchanger (NCX1)'''<br />
'''Second Ca2+ binding domain of the Na,Ca-exchanger (NCX1)'''<br />
==Overview==
==Overview==
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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.
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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.
==About this Structure==
==About this Structure==
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2FWU is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Canis_lupus_familiaris Canis lupus familiaris] with CA as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2FWU OCA].
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2FWU is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Canis_lupus_familiaris Canis lupus familiaris] with <scene name='pdbligand=CA:'>CA</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FWU OCA].
==Reference==
==Reference==
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[[Category: Aelen, J.]]
[[Category: Aelen, J.]]
[[Category: Hilge, M.]]
[[Category: Hilge, M.]]
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[[Category: Vuister, G.W.]]
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[[Category: Vuister, G W.]]
[[Category: CA]]
[[Category: CA]]
[[Category: beta-bulge]]
[[Category: beta-bulge]]
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[[Category: greek key]]
[[Category: greek key]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 10:49:05 2007''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:25:55 2008''

Revision as of 15:25, 21 February 2008


2fwu

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Second Ca2+ binding domain of the Na,Ca-exchanger (NCX1)

Overview

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.

About this Structure

2FWU is a Single protein structure of sequence from Canis lupus familiaris with as ligand. Full crystallographic information is available from OCA.

Reference

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

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