| First Author | Iyer S | Year | 2016 |
| Journal | Nat Commun | Volume | 7 |
| Pages | 11734 | PubMed ID | 27217060 |
| Mgi Jnum | J:236875 | Mgi Id | MGI:5810031 |
| Doi | 10.1038/ncomms11734 | Citation | Iyer S, et al. (2016) Identification of an activation site in Bak and mitochondrial Bax triggered by antibodies. Nat Commun 7:11734 |
| abstractText | During apoptosis, Bak and Bax are activated by BH3-only proteins binding to the alpha2-alpha5 hydrophobic groove; Bax is also activated via a rear pocket. Here we report that antibodies can directly activate Bak and mitochondrial Bax by binding to the alpha1-alpha2 loop. A monoclonal antibody (clone 7D10) binds close to alpha1 in non-activated Bak to induce conformational change, oligomerization, and cytochrome c release. Anti-FLAG antibodies also activate Bak containing a FLAG epitope close to alpha1. An antibody (clone 3C10) to the Bax alpha1-alpha2 loop activates mitochondrial Bax, but blocks translocation of cytosolic Bax. Tethers within Bak show that 7D10 binding directly extricates alpha1; a structural model of the 7D10 Fab bound to Bak reveals the formation of a cavity under alpha1. Our identification of the alpha1-alpha2 loop as an activation site in Bak paves the way to develop intrabodies or small molecules that directly and selectively regulate these proteins. |
