CALB1 binds 4xCa2+

Calbindin (CALB1, aka D-28K, CAB27) is a calcium binding protein with six EF hand domains, functions as both a calcium buffer and a sensor protein and plays a vital role in neurological function. CALB1 binds four calcium ions at its four functional calcium-binding sites (EF hands 1,3,4 and 5), subsequently undergoing a conformational change. EF hands 2 and 6 are known not to bind calcium (Kojetin et al. 2006, Hobbs et al. 2009). Cholinergic neurons of the basal forebrain (BFCN) are selectively vulnerable in Alzheimer's disease (AD). Most of the BFCN in the human brain contain CALB1 and a large proportion lose their CALB1 in the course of normal aging. The BFCN which degenerate in AD lack CALB1, depriving neurons of the capacity to buffer high levels of intracellular calcium and thus leaving them vulnerable to pathological processes, such as those in AD, which can cause increased intracellular calcium, leading to their degeneration (Geula et al. 2003, Ahmadian et al. 2015).

钙结合蛋白Calbindin（又称CALB1、D-28K、CAB27）具备六个EF手结构域，兼具钙缓冲和感应蛋白的功能，并在神经功能中发挥着至关重要的作用。CALB1在其四个功能钙结合位点（EF手1、3、4和5）上结合四个钙离子，随后发生构象变化。已知EF手2和6不具备结合钙的能力（参见Kojetin等，2006年；Hobbs等，2009年）。在阿尔茨海默病（AD）中，基底前脑的胆碱能神经元（BFCN）具有选择性易损性。人类大脑中的大多数BFCN都含有CALB1，且在正常老化过程中，大部分BFCN会丢失其CALB1。在AD中退化的BFCN缺乏CALB1，剥夺了神经元缓冲细胞内高浓度钙离子的能力，因此使其易受病理过程的影响，如AD中的病理过程，这些过程可导致细胞内钙离子浓度增加，进而导致其退化（参见Geula等，2003年；Ahmadian等，2015年）。