title: Structural insights into the calcium-dependent interaction between calbindin-D28K and caspase-3.
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 Ca(2+)-dependent fashion. Molecular docking and conformational sampling studies of the Ca(2+)-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.
authors.affiliation: Department of Molecular and Structural Biochemistry, North Carolina State University, 128 Polk Hall, Raleigh, NC 27695, United States.
authors.forename: Benjamin G
authors.initials: BG
authors.lastname: Bobay
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Stewart
authors.forename: Ashley T
authors.initials: AT
authors.lastname: Tucker
authors.forename: Richele J
authors.initials: RJ
authors.lastname: Thompson
authors.forename: Kristen M
authors.initials: KM
authors.lastname: Varney
authors.forename: John
authors.initials: J
authors.lastname: Cavanagh
mesh_terms: D064026:Calbindins; D002118:Calcium / Q000378:metabolism*; D053148:Caspase 3 / Q000737:chemistry* / Q000378:metabolism*; D004789:Enzyme Activation; D006860:Hydrogen Bonding; D062105:Molecular Docking Simulation; D011485:Protein Binding; D011487:Protein Conformation; D064030:S100 Calcium Binding Protein G / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D064026:Calbindins; D064030:S100 Calcium Binding Protein G; D053148:Caspase 3; D002118:Calcium