期刊
CELL DEATH AND DIFFERENTIATION
卷 19, 期 4, 页码 661-670出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/cdd.2011.138
关键词
apoptosis; Bax; BH3 domain; heterodimer; oligomer; mitochondria
资金
- National Health and Medical Research Council of Australia [575559, 637335]
- Association for International Cancer Research [10-230]
- Australian Government IRISS
- Victorial State Government OIS
- Worldwide Cancer Research [10-0230] Funding Source: researchfish
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
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