How does regulatory Ca2+ regulate the Na+-Ca2+ exchanger?
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.
Chaptal
Vincent
V
Department of Physiology, University of California at Los Angeles, Los Angeles, California, USA.
Besserer
Gabriel Mercado
GM
Ottolia
Michela
M
Nicoll
Debora A
DA
Cascio
Duilio
D
Philipson
Kenneth D
KD
Abramson
Jeff
J
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
D008055:Lipids; D019831:Sodium-Calcium Exchanger; C110374:sodium-calcium exchanger 1; D002118:Calcium