| First Author | Mandal T | Year | 2016 |
| Journal | Sci Rep | Volume | 6 |
| Pages | 30763 | PubMed ID | 27488021 |
| Mgi Jnum | J:313851 | Mgi Id | MGI:6225541 |
| Doi | 10.1038/srep30763 | Citation | Mandal T, et al. (2016) Assembly of Bak homodimers into higher order homooligomers in the mitochondrial apoptotic pore. Sci Rep 6:30763 |
| abstractText | In mitochondrial apoptosis, Bak is activated by death signals to form pores of unknown structure on the mitochondrial outer membrane via homooligomerization. Cytochrome c and other apoptotic factors are released from the intermembrane space through these pores, initiating downstream apoptosis events. Using chemical crosslinking and double electron electron resonance (DEER)-derived distance measurements between specific structural elements in Bak, here we clarify how the Bak pore is assembled. We propose that previously described BH3-in-groove homodimers (BGH) are juxtaposed via the 'alpha3/alpha5' interface, in which the C-termini of helices alpha3 and alpha5 are in close proximity between two neighboring Bak homodimers. This interface is observed concomitantly with the well-known 'alpha6:alpha6' interface. We also mapped the contacts between Bak homodimers and the lipid bilayer based on EPR spectroscopy topology studies. Our results suggest a model for the lipidic Bak pore, whereby the mitochondrial targeting C-terminal helix does not change topology to accommodate the lining of the pore lumen by BGH. |
