title: How does regulatory Ca2+ regulate the Na+-Ca2+ exchanger?
abstract: Spatial and temporal regulation of intracellular Ca2+ concentrations is a fundamental requirement for life. The mammalian cardiac Na+-Ca2+ exchanger serves as the main mechanism for Ca2+ efflux after heart contraction. Exchange activity is highly regulated by intracellular Ca2+, 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 Ca2+. Together with mutational analysis of the Ca2+ binding sites, this study reveals the crucial role of one of the two bound Ca2+ ions and helps propose hypotheses on the mechanism of regulation of the exchanger.
authors.affiliation: Department of Physiology, University of California at Los Angeles, Los Angeles, California, USA.
authors.forename: Vincent
authors.initials: V
authors.lastname: Chaptal
authors.forename: Gabriel Mercado
authors.initials: GM
authors.lastname: Besserer
authors.forename: Michela
authors.initials: M
authors.lastname: Ottolia
authors.forename: Debora A
authors.initials: DA
authors.lastname: Nicoll
authors.forename: Duilio
authors.initials: D
authors.lastname: Cascio
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Philipson
authors.forename: Jeff
authors.initials: J
authors.lastname: Abramson
mesh_terms: D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000737:chemistry; D018360:Crystallography, X-Ray; D004252:DNA Mutational Analysis; D005786:Gene Expression Regulation; D006801:Humans; D008055:Lipids / Q000737:chemistry; D008968:Molecular Conformation; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D019831:Sodium-Calcium Exchanger / Q000378:metabolism / Q000502:physiology*; D013997:Time Factors
chemical_list: D008055:Lipids; D019831:Sodium-Calcium Exchanger; C110374:sodium-calcium exchanger 1; D002118:Calcium