2K7W

BAX Activation is Initiated at a Novel Interaction Site

2K7W の概要

• エントリーDOI: 10.2210/pdb2k7w/pdb
• 関連するPDBエントリー: 1F16
• 分子名称: Apoptosis regulator BAX, Bcl-2-like protein 11 (2 entities in total)
• 機能のキーワード: bax, bim, bh3, bcl-2, apoptosis
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: 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
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 23664.07

構造登録者

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. (登録日: 2008-08-27, 公開日: 2008-10-21, 最終更新日: 2024-05-22)

主引用文献

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

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: 18948948
DOI: 10.1038/nature07396

実験手法

SOLUTION NMR