| First Author | Bogner C | Year | 2020 |
| Journal | Mol Cell | Volume | 77 |
| Issue | 4 | Pages | 901-912.e9 |
| PubMed ID | 32001105 | Mgi Jnum | J:347523 |
| Mgi Id | MGI:6400698 | Doi | 10.1016/j.molcel.2019.12.025 |
| Citation | Bogner C, et al. (2020) Allosteric Regulation of BH3 Proteins in Bcl-xL Complexes Enables Switch-like Activation of Bax. Mol Cell 77(4):901-912.e9 |
| abstractText | Current models of apoptosis regulation by the Bcl-2 family of proteins postulate that heterodimeric interactions between family members determine whether Bax and Bak are activated to trigger cell death. Thus, the relative abundance and binding affinities between pro- and anti-apoptotic proteins determines the outcome of these interactions. Examination of these interactions using purified mitochondria and liposomes with full-length recombinant proteins revealed that Bcl-xL inhibits apoptosis as a higher-order complex that binds multiple BH3 proteins. Allosteric regulation of this complex by the BH3 sensitizer Bad confers switch-like activity to the indirect activation of Bax. The BH3 activator cBid sequestered by Bcl-xL complexes changes from an inactive to an active form while bound to a Bcl-xL complex only when Bad is also bound. Bcl-xL complexes enable Bad to function as a non-competitive inhibitor of Bcl-xL and allosterically activate cBid, dramatically enhancing the pro-apoptotic potency of Bad. |
