2qvm: Difference between revisions
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'''The second Ca2+-binding domain of the Na+-Ca2+ exchanger is essential for regulation: crystal structures and mutational analysis''' | {{Structure | ||
|PDB= 2qvm |SIZE=350|CAPTION= <scene name='initialview01'>2qvm</scene>, resolution 1.703Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=CA:CALCIUM ION'>CA</scene> | |||
|ACTIVITY= | |||
|GENE= SLC8A1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9615 Canis lupus familiaris]) | |||
}} | |||
'''The second Ca2+-binding domain of the Na+-Ca2+ exchanger is essential for regulation: crystal structures and mutational analysis''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
2QVM is a [ | 2QVM 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=2QVM OCA]. | ||
==Reference== | ==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:[http:// | 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:[http://www.ncbi.nlm.nih.gov/pubmed/17962412 17962412] | ||
[[Category: Canis lupus familiaris]] | [[Category: Canis lupus familiaris]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: ncx]] | [[Category: ncx]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 18:29:59 2008'' | ||
Revision as of 16:29, 20 March 2008
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| 2qvm, resolution 1.703Å | |||||||||||||
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| Ligands: | CA | ||||||||||||
| Gene: | SLC8A1 (Canis lupus familiaris) | ||||||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||||||
The second Ca2+-binding domain of the Na+-Ca2+ exchanger is essential for regulation: crystal structures and mutational analysis
Overview
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.
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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