7M5C
Crystal Structure of human BAK in complex with WT BAK BH3 peptide
7M5C の概要
エントリーDOI | 10.2210/pdb7m5c/pdb |
分子名称 | Bcl-2 homologous antagonist/killer, COPPER (II) ION, SULFATE ION, ... (4 entities in total) |
機能のキーワード | protein-peptide complex, apoptosis |
由来する生物種 | Homo sapiens (Human) 詳細 |
タンパク質・核酸の鎖数 | 20 |
化学式量合計 | 215039.63 |
構造登録者 | |
主引用文献 | Singh, G.,Guibao, C.D.,Seetharaman, J.,Aggarwal, A.,Grace, C.R.,McNamara, D.E.,Vaithiyalingam, S.,Waddell, M.B.,Moldoveanu, T. Structural basis of BAK activation in mitochondrial apoptosis initiation. Nat Commun, 13:250-250, 2022 Cited by PubMed Abstract: BCL-2 proteins regulate mitochondrial poration in apoptosis initiation. How the pore-forming BCL-2 Effector BAK is activated remains incompletely understood mechanistically. Here we investigate autoactivation and direct activation by BH3-only proteins, which cooperate to lower BAK threshold in membrane poration and apoptosis initiation. We define in trans BAK autoactivation as the asymmetric "BH3-in-groove" triggering of dormant BAK by active BAK. BAK autoactivation is mechanistically similar to direct activation. The structure of autoactivated BAK BH3-BAK complex reveals the conformational changes leading to helix α1 destabilization, which is a hallmark of BAK activation. Helix α1 is destabilized and restabilized in structures of BAK engaged by rationally designed, high-affinity activating and inactivating BID-like BH3 ligands, respectively. Altogether our data support the long-standing hit-and-run mechanism of BAK activation by transient binding of BH3-only proteins, demonstrating that BH3-induced structural changes are more important in BAK activation than BH3 ligand affinity. PubMed: 35017502DOI: 10.1038/s41467-021-27851-y 主引用文献が同じPDBエントリー |
実験手法 | X-RAY DIFFRACTION (3.06 Å) |
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