Bax dimerizes via a symmetric BH3:groove interface during apoptosis

Dewson, G; Ma, S; Frederick, P; Hockings, C; Tan, I; Kratina, T; Kluck, RM

Author(s): Dewson, G; Ma, S; Frederick, P; Hockings, C; Tan, I; Kratina, T; Kluck, RM;
Details: Publication Year 2012-04,Volume 19,Issue #4,Page 661-670
Journal Title: CELL DEATH AND DIFFERENTIATION
Publication Type: Journal Article
Abstract: During apoptotic cell death, Bax and Bak change conformation and homo-oligomerize to permeabilize mitochondria. We recently reported that Bak homodimerizes via an interaction between the BH3 domain and hydrophobic surface groove, that this BH3:groove interaction is symmetric, and that symmetric dimers can be linked via the alpha 6-helices to form the high order oligomers thought responsible for pore formation. We now show that Bax also dimerizes via a BH3:groove interaction after apoptotic signaling in cells and in mitochondrial fractions. BH3:groove dimers of Bax were symmetric as dimers but not higher order oligomers could be linked by cysteine residues placed in both the BH3 and groove. The BH3:groove interaction was evident in the majority of mitochondrial Bax after apoptotic signaling, and correlated strongly with cytochrome c release, supporting its central role in Bax function. A second interface between the Bax alpha 6-helices was implicated by cysteine linkage studies, and could link dimers to higher order oligomers. We also found that a population of Bax: Bak heterodimers generated during apoptosis formed via a BH3:groove interaction, further demonstrating that Bax and Bak oligomerize via similar mechanisms. These findings highlight the importance of BH3:groove interactions in apoptosis regulation by the Bcl-2 protein family. Cell Death and Differentiation (2012) 19, 661-670; doi:10.1038/cdd.2011.138; published online 21 October 2011
Publisher: NATURE PUBLISHING GROUP
Keywords: PROSURVIVAL BCL-2 PROTEINS; BH3 DOMAIN; MITOCHONDRIAL APOPTOSIS; CONFORMATIONAL-CHANGES; MEMBRANE INSERTION; FAMILY-MEMBERS; HOMO-OLIGOMERS; CYTOCHROME-C; ACTIVATION; BINDING
Publisher's Version: https://doi.org/10.1038/cdd.2011.138
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2012-04-01 12:00:00