| First Author | Alsop AE | Year | 2015 |
| Journal | Nat Commun | Volume | 6 |
| Pages | 6841 | PubMed ID | 25880232 |
| Mgi Jnum | J:222713 | Mgi Id | MGI:5645418 |
| Doi | 10.1038/ncomms7841 | Citation | Alsop AE, et al. (2015) Dissociation of Bak alpha1 helix from the core and latch domains is required for apoptosis. Nat Commun 6:6841 |
| abstractText | During apoptosis, Bak permeabilizes mitochondria after undergoing major conformational changes, including poorly defined N-terminal changes. Here, we characterize those changes using 11 antibodies that were epitope mapped using peptide arrays and mutagenesis. After Bak activation by Bid, epitopes throughout the alpha1 helix are exposed indicating complete dissociation of alpha1 from alpha2 in the core and from alpha6-alpha8 in the latch. Moreover, disulfide tethering of alpha1 to alpha2 or alpha6 blocks cytochrome c release, suggesting that alpha1 dissociation is required for further conformational changes during apoptosis. Assaying epitope exposure when alpha1 is tethered shows that Bid triggers alpha2 movement, followed by alpha1 dissociation. However, alpha2 reaches its final position only after alpha1 dissociates from the latch. Thus, alpha1 dissociation is a key step in unfolding Bak into three major components, the N terminus, the core (alpha2-alpha5) and the latch (alpha6-alpha8). |
