How Does Regulatory Ca2+ Regulate the Na+-Ca2+ Exchanger?

Spatial and temporal regulation of intracellular Ca 2+ concentrations is a fundamental requirement for life. The mammalian cardiac Na + -Ca 2+ exchanger serves as the main mechanism for Ca 2+ efflux after heart contraction. Exchange activity is highly regulated by intracellular Ca 2+ , which binds t...

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Bibliographic Details
Published in:Channels (Austin, Tex.) Tex.), 2007-11, Vol.1 (6), p.397-399
Main Authors: Chaptal, Vincent, Besserer, Gabriel Mercado, Ottolia, Michela, Nicoll, Debora A., Cascio, Duilio, Philipson, Kenneth D., Abramson, Jeff
Format: Article
Language:English
Subjects:
Animals
Binding
Binding Sites
Biology
Bioscience
Calcium
Calcium - chemistry
Cancer
Cell
Crystallography, X-Ray
Cycle
DNA Mutational Analysis
Gene Expression Regulation
Humans
Landes
Lipids - chemistry
Molecular Conformation
Organogenesis
Protein Structure, Tertiary
Proteins
Signal Transduction
Sodium-Calcium Exchanger - metabolism
Sodium-Calcium Exchanger - physiology
Time Factors
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Summary:Spatial and temporal regulation of intracellular Ca 2+ concentrations is a fundamental requirement for life. The mammalian cardiac Na + -Ca 2+ exchanger serves as the main mechanism for Ca 2+ efflux after heart contraction. Exchange activity is highly regulated by intracellular Ca 2+ , which binds two regulatory domains (CBD1 and CBD2) and triggers the full activity of the exchanger. We solved the X-ray crystallographic structure of CBD2 in the presence and absence of Ca 2+ . Together with mutational analysis of the Ca 2+ binding sites, this study reveals the crucial role of one of the two bound Ca 2+ ions and helps propose hypotheses on the mechanism of regulation of the exchanger.
ISSN:1933-6950
1933-6969
DOI:10.4161/chan.1.6.5640