2qvk
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(New page: 200px<br /><applet load="2qvk" size="350" color="white" frame="true" align="right" spinBox="true" caption="2qvk, resolution 1.451Å" /> '''The second Ca2+-bin...)
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Revision as of 09:03, 23 January 2008
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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-Aresolution) 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
2QVK 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., Mercado Besserer G, Ottolia M, Nicoll DA, Chaptal V, Cascio D, Philipson KD, Abramson J, Proc Natl Acad Sci U S A. 2007 Oct 25;. PMID:17962412
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