2K7W
BAX Activation is Initiated at a Novel Interaction Site
Summary for 2K7W
| Entry DOI | 10.2210/pdb2k7w/pdb |
| Related | 1F16 |
| Descriptor | Apoptosis regulator BAX, Bcl-2-like protein 11 (2 entities in total) |
| Functional Keywords | bax, bim, bh3, bcl-2, apoptosis |
| Biological source | Homo sapiens (human) |
| Cellular location | Isoform Alpha: Mitochondrion membrane; Single-pass membrane protein. Isoform Beta: Cytoplasm. Isoform Gamma: Cytoplasm. Isoform Delta: Cytoplasm (Potential): Q07812 Endomembrane system; Peripheral membrane protein (By similarity). Isoform BimEL: Mitochondrion. Isoform BimL: Mitochondrion. Isoform BimS: Mitochondrion. Isoform Bim-alpha1: Mitochondrion: O43521 |
| Total number of polymer chains | 2 |
| Total formula weight | 23664.07 |
| Authors | Gavathiotis, E.,Suzuki, M.,Davis, M.L.,Pitter, K.,Bird, G.H.,Katz, S.G.,Tu, H.C.,Kim, H.,Cheng, E.H.,Tjandra, N.,Walensky, L.D. (deposition date: 2008-08-27, release date: 2008-10-21, Last modification date: 2024-05-22) |
| Primary citation | Gavathiotis, E.,Suzuki, M.,Davis, M.L.,Pitter, K.,Bird, G.H.,Katz, S.G.,Tu, H.C.,Kim, H.,Cheng, E.H.,Tjandra, N.,Walensky, L.D. BAX activation is initiated at a novel interaction site. Nature, 455:1076-1081, 2008 Cited by PubMed Abstract: BAX is a pro-apoptotic protein of the BCL-2 family that is stationed in the cytosol until activated by a diversity of stress stimuli to induce cell death. Anti-apoptotic proteins such as BCL-2 counteract BAX-mediated cell death. Although an interaction site that confers survival functionality has been defined for anti-apoptotic proteins, an activation site has not been identified for BAX, rendering its explicit trigger mechanism unknown. We previously developed stabilized alpha-helix of BCL-2 domains (SAHBs) that directly initiate BAX-mediated mitochondrial apoptosis. Here we demonstrate by NMR analysis that BIM SAHB binds BAX at an interaction site that is distinct from the canonical binding groove characterized for anti-apoptotic proteins. The specificity of the human BIM-SAHB-BAX interaction is highlighted by point mutagenesis that disrupts functional activity, confirming that BAX activation is initiated at this novel structural location. Thus, we have now defined a BAX interaction site for direct activation, establishing a new target for therapeutic modulation of apoptosis. PubMed: 18948948DOI: 10.1038/nature07396 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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