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Abstract: 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. Structured summary of protein interactions: Calbindin-D28K and Caspase-3 bind by isothermal titration calorimetry (View interaction) [Copyright &y& Elsevier]

Abstract: Calbindin-D28k is known to function as a calcium-buffering protein in the cell. Moreover, recent evidence shows that it also plays a role as a sensor. Using circular dichroism and NMR, we show that calbindin-D28k undergoes significant conformational changes upon binding calcium, whereas only minor changes occur when binding target peptides in its Ca2+-loaded state. NMR experiments also identify residues that undergo chemical shift changes as a result of peptide binding. The subsequent use of computational protein–protein docking protocols produce a model describing the interaction interface between calbindin-D28k and its target peptides. [Copyright &y& Elsevier]