The regulation of apoptosis involves a complicated cascade requiring numerous protein interactions including the pro-apoptotic executioner protein caspase-3 and the anti-apoptotic calcium-binding protein calbindin-D28K. Using isothermal titration calorimetry, we show that calbindin-D28K binds caspase-3 in a Ca2+-dependent fashion. Molecular docking and conformational sampling studies of the Ca2+-loaded capase-3/calbindin-D28K interaction were performed in order to isolate potentially crucial intermolecular contacts. Residues in the active site loops of caspase-3 and EF-hands 1 and 2 of calbindin-D28K were shown to be critical to the interaction. Based on these studies, a model is proposed to help understand how calbindin-D28K may deactivate caspase-3 upon binding.
Structural insights into the calcium-dependent interaction between calbindin-D28K and caspase-3
Bobay, B. G., Stewart, A. L., Tucker, A. T., Thompson, R. J., Varney, K. M., & Cavanagh, J. (2012). Structural insights into the calcium-dependent interaction between calbindin-D28K and caspase-3. FEBS Letters, 586(20), 3582-3589. https://doi.org/10.1016/j.febslet.2012.08.032