6CKV

Solution NMR structure of human BOK

6CKV の概要

• エントリーDOI: 10.2210/pdb6ckv/pdb
• 関連するPDBエントリー: 5WDD
• NMR情報: BMRB: 30423
• 分子名称: Bcl-2-related ovarian killer protein (1 entity in total)
• 機能のキーワード: apoptosis
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 17186.01

構造登録者

Grace, C.R.,Zheng, J.,Moldoveanu, T. (登録日: 2018-03-01, 公開日: 2018-05-09, 最終更新日: 2024-05-15)

主引用文献

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

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: 29768206
DOI: 10.1016/j.celrep.2018.04.060

実験手法

SOLUTION NMR