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Updated: Sep 5, 2026

Examining BCL-2 Family Function with Large Unilamellar Vesicles
Published on: October 5, 2012
Direct binding of the C-terminal sequences of Bim and Bak contributes to efficient Bak activation
Dang Nguyen1,2, Sabina Trebinjac1,3, Tobias B Beigl4
1Biological Sciences Platform, Sunnybrook Research Institute, Toronto, ON, Canada.
Abstract:
Apoptosis is regulated by Bcl-2 family of proteins through direct binding interactions at the mitochondrial outer membrane. Bak, a key cellular executioner protein in this family, differs from the other executioner proteins Bax and Bok in that it is constitutively localized at the mitochondrial outer membrane via its C-terminal sequence (CTS). Binding of the BH3-only protein Bim triggers conformational changes in Bak that lead to oligomerization and mitochondrial membrane permeabilization. However, the molecular mechanism by which Bim activates Bak remains incompletely understood. Here we demonstrate both in vitro and in cells, that efficient Bim-mediated activation of Bak requires not only the binding of the BH3-motif of Bim to the canonical BH3-binding groove of Bak, but also sequence specific, direct binding of the Bim-CTS to the Bak-CTS. These findings reveal an unexpected contribution of the Bak-CTS to the molecular control of Bak activation during apoptosis.
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