Hilge Mark, Aelen Jan, Perrakis Anastassis, Vuister Geerten W
Department of Biophysical Chemistry, Institute for Molecules and Materials, Radboud University Nijmegen, Toernooiveld 1, 6525 ED Nijmegen, The Netherlands.
Ann N Y Acad Sci. 2007 Mar;1099:7-15. doi: 10.1196/annals.1387.030. Epub 2007 Mar 8.
Binding of Na+ and Ca2+ ions to the large cytosolic loop of the Na+/Ca2+ exchanger (NCX) regulates its ion transport across the plasma membrane. 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 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 sevenfold 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.
钠离子和钙离子与钠钙交换体（NCX）的大胞质环结合，调节其跨质膜的离子转运。我们确定了两个钙结合结构域（CBD1和CBD2）的溶液结构，它们与一个α-连环蛋白样结构域（CLD）共同构成调节性交换体环。CBD1和CBD2构成了一种新型钙结合基序，在结合钙的状态下非常相似。引人注目的是，在没有钙离子的情况下，CBD1的上半部分会展开，而CBD2则保持其结构完整性。再加上对钙离子的亲和力高出七倍，这表明CBD1是主要的钙离子传感器。任一结构域中的特定点突变在很大程度上允许它们的功能互换，并揭示了NCX中钙离子传感的潜在机制。
