6CKV
Solution NMR structure of human BOK
Summary for 6CKV
| Entry DOI | 10.2210/pdb6ckv/pdb |
| Related | 5WDD |
| NMR Information | BMRB: 30423 |
| Descriptor | Bcl-2-related ovarian killer protein (1 entity in total) |
| Functional Keywords | apoptosis |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 17186.01 |
| Authors | Grace, C.R.,Zheng, J.,Moldoveanu, T. (deposition date: 2018-03-01, release date: 2018-05-09, Last modification date: 2024-05-15) |
| Primary citation | Zheng, J.H.,Grace, C.R.,Guibao, C.D.,McNamara, D.E.,Llambi, F.,Wang, Y.M.,Chen, T.,Moldoveanu, T. Intrinsic Instability of BOK Enables Membrane Permeabilization in Apoptosis. Cell Rep, 23:2083-2094.e6, 2018 Cited by PubMed Abstract: The effector B cell lymphoma-2 (BCL-2) protein BCL-2 ovarian killer (BOK) induces mitochondrial outer membrane permeabilization (MOMP) to initiate apoptosis upon inhibition of the proteasome. How BOK mediates MOMP is mechanistically unknown. The NMR structure of the BCL-2 core of human BOK reveals a conserved architecture with an atypical hydrophobic groove that undergoes conformational exchange. Remarkably, the BCL-2 core of BOK spontaneously associates with purified mitochondria to release cytochrome c in MOMP assays. Alanine substitution of a unique glycine in helix α1 stabilizes BOK, as shown by thermal shift and urea denaturation analyses, and significantly inhibits MOMP, liposome permeabilization, and cell death. Activated BID does not activate WT BOK or the stabilized alanine mutant to promote cell death. We propose that BOK-mediated membrane permeabilization is governed in part by its unique metastability of the hydrophobic groove and helix α1 and not through activation by BH3 ligands. PubMed: 29768206DOI: 10.1016/j.celrep.2018.04.060 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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