Ca2+-regulation in the Na+/Ca2+ exchanger involves two
Markedly Different Ca2+ Sensors
The plasma membrane Na+/Ca2+ exchanger (NCX) is
almost certainly the major Ca2+ extrusion mechanism in
cardiac myocytes. Binding of Na+ and Ca2+ ions to its large
cytosolic loop regulates ion transport of the exchanger. We
determined the solution structures of two Ca2+ binding
domains (CBD1 and CBD2) that, together with an
α-catenin-like domain (CLD), form the regulatory
exchanger loop. CBD1 and CBD2 constitute a novel Ca2+
binding motif and are very similar in the Ca2+-bound state.
Strikingly, in the absence of Ca2+ the upper half of CBD1
unfolds while CBD2 maintains its structural integrity.
Together with a seven-fold higher affinity for Ca2+ this
suggests that CBD1 is the primary Ca2+ sensor. Specific
point mutations in either domain largely allow the
interchange of their functionality and uncover the
mechanism underlying Ca2+ sensing in NCX.
CBD1-domain PDB code: 2FWS (
Download) and CBD2-domain PDB code:
2FWU (
Download)
■ Hilge, M., Aelen, J.M.A., Vuister, G.W. (2006)
“Ca2+-regulation in the Na+/Ca2+ exchanger involves
two Markedly Different Ca2+ Sensors”,
Mol.
Cell 22, 15-25.
