Structural insights into the calcium-dependent interaction between calbindin-D28K and caspase-3.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Bobay, BG; Stewart, AL; Tucker, AT; Thompson, RJ; Varney, KM; Cavanagh, J

Published Date

  • October 2012

Published In

Volume / Issue

  • 586 / 20

Start / End Page

  • 3582 - 3589

PubMed ID

  • 22982862

Electronic International Standard Serial Number (EISSN)

  • 1873-3468

International Standard Serial Number (ISSN)

  • 0014-5793

Digital Object Identifier (DOI)

  • 10.1016/j.febslet.2012.08.032


  • eng