Assembly of Bak homodimers into higher order homooligomers in the mitochondrial apoptotic pore Journal Article
| Authors: | Mandal, T.; Shin, S.; Aluvila, S.; Chen, H. C.; Grieve, C.; Choe, J. Y.; Cheng, E. H.; Hustedt, E. J.; Oh, K. J. |
| Article Title: | Assembly of Bak homodimers into higher order homooligomers in the mitochondrial apoptotic pore |
| Abstract: | 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 â α3/α5' interface, in which the C-termini of helices α3 and α5 are in close proximity between two neighboring Bak homodimers. This interface is observed concomitantly with the well-known 'α6:α6' 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. |
| Journal Title: | Scientific Reports |
| Volume: | 6 |
| ISSN: | 2045-2322 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2016-08-04 |
| Start Page: | 30763 |
| Language: | English |
| DOI: | 10.1038/srep30763 |
| PROVIDER: | scopus |
| PMCID: | PMC4973285 |
| PUBMED: | 27488021 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 September 2016 -- Source: Scopus |
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