CALB1 binds 4xCa2+

Stable Identifier
Homo sapiens
Locations in the PathwayBrowser

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).

Literature References
PubMed ID Title Journal Year
16799559 Structure, binding interface and hydrophobic transitions of Ca2+-loaded calbindin-D(28K)

Kojetin, DJ, Venters, RA, Kordys, DR, Thompson, RJ, Kumar, R, Cavanagh, J

Nat. Struct. Mol. Biol. 2006
12454989 Loss of calbindin-D28k from aging human cholinergic basal forebrain: relation to neuronal loss

Geula, C, Bu, J, Nagykery, N, Scinto, LF, Chan, J, Joseph, J, Parker, R, Wu, CK

J. Comp. Neurol. 2003
26417681 Loss of calbindin-D28K is associated with the full range of tangle pathology within basal forebrain cholinergic neurons in Alzheimer's disease

Ahmadian, SS, Rezvanian, A, Peterson, M, Weintraub, S, Bigio, EH, Mesulam, MM, Geula, C

Neurobiol. Aging 2015
19658395 Structural characterization of the conformational change in calbindin-D28k upon calcium binding using differential surface modification analyzed by mass spectrometry

Hobbs, CA, Deterding, LJ, Perera, L, Bobay, BG, Thompson, RJ, Darden, TA, Cavanagh, J, Tomer, KB

Biochemistry 2009
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