2fwu
Second Ca2+ binding domain of the Na,Ca-exchanger (NCX1)Second Ca2+ binding domain of the Na,Ca-exchanger (NCX1)
Structural highlights
Function[NAC1_CANFA] Rapidly transports Ca(2+) during excitation-contraction coupling. Ca(2+) is extruded from the cell during relaxation so as to prevent overloading of intracellular stores. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe 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 alpha-catenin-like domain (CLD), form the regulatory exchanger loop. CBD1 and CBD2 are very similar in the Ca2+ bound state and describe the Calx-beta motif. Strikingly, in the absence of Ca2+, the upper half of CBD1 unfolds while CBD2 maintains its structural integrity. Together with a 7-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. Ca2+ regulation in the Na+/Ca2+ exchanger involves two markedly different Ca2+ sensors.,Hilge M, Aelen J, Vuister GW Mol Cell. 2006 Apr 7;22(1):15-25. PMID:16600866[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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