| First Author | Dewson G | Year | 2012 |
| Journal | Cell Death Differ | Volume | 19 |
| Issue | 4 | Pages | 661-70 |
| PubMed ID | 22015607 | Mgi Jnum | J:203074 |
| Mgi Id | MGI:5524187 | Doi | 10.1038/cdd.2011.138 |
| Citation | Dewson G, et al. (2012) Bax dimerizes via a symmetric BH3:groove interface during apoptosis. Cell Death Differ 19(4):661-70 |
| abstractText | 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 alpha6-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 alpha6-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. |
