8IVB

K113-Ubiquitinated BAK

8IVB の概要

• エントリーDOI: 10.2210/pdb8ivb/pdb
• 分子名称: Ubiquitin, Bcl-2 homologous antagonist/killer (2 entities in total)
• 機能のキーワード: pro-apoptotic bcl-2 proteins, apoptosis
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 27547.13

構造登録者

Dong, X.,Cheng, P.,Hou, Y.Z.,Chen, Y.K.,Liu, Z. (登録日: 2023-03-26, 公開日: 2024-01-31, 最終更新日: 2024-10-16)

主引用文献

Cheng, P.,Hou, Y.,Bian, M.,Fang, X.,Liu, Y.,Rao, Y.,Cao, S.,Liu, Y.,Zhang, S.,Chen, Y.,Dong, X.,Liu, Z.
Parkin-mediated ubiquitination inhibits BAK apoptotic activity by blocking its canonical hydrophobic groove.
Commun Biol, 6:1260-1260, 2023

PubMed Abstract: BAK permeabilizes the mitochondrial outer membrane, causing apoptosis. This apoptotic activity of BAK is stimulated by binding prodeath activators within its canonical hydrophobic groove. Parkin, an E3 ubiquitin (Ub) ligase, can ubiquitinate BAK, which inhibits BAK apoptotic activity. However, the molecular mechanism underlying the inhibition of ubiquitination remains structurally uncharacterized. Here, we utilize truncated and soluble BAK to construct a mimetic of K113-ubiquitinated BAK (disulfide-linked Ub ~ BAK) and further present its NMR-derived structure model. The classical L8-I44-H68-V70 hydrophobic patch of the conjugated Ub subunit binds within the canonical hydrophobic groove of BAK. This Ub occludes the binding of prodeath BID activators in the groove and impairs BID-triggered BAK activation and membrane permeabilization. Reduced interaction between Ub and BAK subunits allows BID to activate K113-ubiquitinated BAK. These mechanistic insights suggest a nonsignaling function of Ub in that it directly antagonizes stimuli targeting Ub-modified proteins rather than by recruiting downstream partners for cellular messaging.

PubMed: 38087033
DOI: 10.1038/s42003-023-05650-z

実験手法

SOLUTION NMR