2qvm

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{{STRUCTURE_2qvm| PDB=2qvm | SCENE= }}
{{STRUCTURE_2qvm| PDB=2qvm | SCENE= }}
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'''The second Ca2+-binding domain of the Na+-Ca2+ exchanger is essential for regulation: crystal structures and mutational analysis'''
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===The second Ca2+-binding domain of the Na+-Ca2+ exchanger is essential for regulation: crystal structures and mutational analysis===
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==Overview==
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The Na(+)-Ca(2+) exchanger plays a central role in cardiac contractility by maintaining Ca(2+) homeostasis. Two Ca(2+)-binding domains, CBD1 and CBD2, located in a large intracellular loop, regulate activity of the exchanger. Ca(2+) binding to these regulatory domains activates the transport of Ca(2+) across the plasma membrane. Previously, we solved the structure of CBD1, revealing four Ca(2+) ions arranged in a tight planar cluster. Here, we present structures of CBD2 in the Ca(2+)-bound (1.7-A resolution) and -free (1.4-A resolution) conformations. Like CBD1, CBD2 has a classical Ig fold but coordinates only two Ca(2+) ions in primary and secondary Ca(2+) sites. In the absence of Ca(2+), Lys(585) stabilizes the structure by coordinating two acidic residues (Asp(552) and Glu(648)), one from each of the Ca(2+)-binding sites, and prevents a substantial protein unfolding. We have mutated all of the acidic residues that coordinate the Ca(2+) ions and have examined the effects of these mutations on regulation of exchange activity. Three mutations (E516L, D578V, and E648L) at the primary Ca(2+) site completely remove Ca(2+) regulation, placing the exchanger into a constitutively active state. These are the first data defining the role of CBD2 as a regulatory domain in the Na(+)-Ca(2+) exchanger.
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(as it appears on PubMed at http://www.pubmed.gov), where 17962412 is the PubMed ID number.
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{{ABSTRACT_PUBMED_17962412}}
==About this Structure==
==About this Structure==
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[[Category: Metal binding protein]]
[[Category: Metal binding protein]]
[[Category: Ncx]]
[[Category: Ncx]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 15:45:56 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 20:16:08 2008''

Revision as of 17:16, 28 July 2008

Image:2qvm.png

Template:STRUCTURE 2qvm

The second Ca2+-binding domain of the Na+-Ca2+ exchanger is essential for regulation: crystal structures and mutational analysis

Template:ABSTRACT PUBMED 17962412

About this Structure

2QVM is a Single protein structure of sequence from Canis lupus familiaris. Full crystallographic information is available from OCA.

Reference

The second Ca2+-binding domain of the Na+ Ca2+ exchanger is essential for regulation: crystal structures and mutational analysis., Besserer GM, Ottolia M, Nicoll DA, Chaptal V, Cascio D, Philipson KD, Abramson J, Proc Natl Acad Sci U S A. 2007 Nov 20;104(47):18467-72. Epub 2007 Oct 25. PMID:17962412

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