| First Author | Zhang Z | Year | 2016 |
| Journal | EMBO J | Volume | 35 |
| Issue | 2 | Pages | 208-36 |
| PubMed ID | 26702098 | Mgi Jnum | J:229673 |
| Mgi Id | MGI:5752989 | Doi | 10.15252/embj.201591552 |
| Citation | Zhang Z, et al. (2016) BH3-in-groove dimerization initiates and helix 9 dimerization expands Bax pore assembly in membranes. EMBO J 35(2):208-36 |
| abstractText | Pro-apoptotic Bax induces mitochondrial outer membrane permeabilization (MOMP) by forming oligomers through a largely undefined process. Using site-specific disulfide crosslinking, compartment-specific chemical labeling, and mutational analysis, we found that activated integral membrane Bax proteins form a BH3-in-groove dimer interface on the MOM surface similar to that observed in crystals. However, after the alpha5 helix was released into the MOM, the remaining interface with alpha2, alpha3, and alpha4 helices was rearranged. Another dimer interface was formed inside the MOM by two intersected or parallel alpha9 helices. Combinations of these interfaces generated oligomers in the MOM. Oligomerization was initiated by BH3-in-groove dimerization, without which neither the other dimerizations nor MOMP occurred. In contrast, alpha9 dimerization occurred downstream and was required for release of large but not small proteins from mitochondria. Moreover, the release of large proteins was facilitated by alpha9 insertion into the MOM and localization to the pore rim. Therefore, the BH3-in-groove dimerization on the MOM nucleates the assembly of an oligomeric Bax pore that is enlarged by alpha9 dimerization at the rim. |
