2ME8

Solution Structure of BCL-xL in its p53-bound conformation determined with selective isotope labelling of I,L,V sidechains

2ME8 の概要

• エントリーDOI: 10.2210/pdb2me8/pdb
• 関連するPDBエントリー: 2ME9 2MEJ
• NMR情報: BMRB: 19520
• 分子名称: Bcl-2-like protein 1 (1 entity in total)
• 機能のキーワード: bcl-xl, p53, apoptosis, bcl-2 family, cytoplasmic p53, selective labeling
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Isoform Bcl-X(L): Mitochondrion inner membrane (By similarity): Q07817
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 23669.94

構造登録者

Viacava Follis, A.,Grace, C.R.,Kriwacki, R.W. (登録日: 2013-09-25, 公開日: 2014-04-30, 最終更新日: 2024-05-15)

主引用文献

Follis, A.V.,Llambi, F.,Ou, L.,Baran, K.,Green, D.R.,Kriwacki, R.W.
The DNA-binding domain mediates both nuclear and cytosolic functions of p53.
Nat.Struct.Mol.Biol., 21:535-543, 2014

PubMed Abstract: Under conditions of genotoxic stress, human p53 activates the apoptotic effectors BAX or BAK to result in mitochondrial outer-membrane permeabilization and apoptosis. Antiapoptotic BCL-2 family member BCL-xL opposes this activity by sequestering cytosolic p53 via association with its DNA-binding domain, an interaction enhanced by p53 tetramerization. Here we characterized the BCL-xL-p53 complex by NMR spectroscopy and modulated it through mutagenesis to determine the relative contributions of BCL-xL's interactions with p53 or other BCL-2 family proteins to the BCL-xL-dependent inhibition of UV irradiation-induced apoptosis. Under our experimental conditions, one-third of the antiapoptotic activity of BCL-xL was mediated by p53 sequestration and the remaining two-thirds through sequestration of proapoptotic BCL-2 family members. Our studies define the contributions of cytosolic p53 to UV irradiation-induced apoptosis and provide opportunities to explore its contributions to other p53-dependent apoptotic signaling pathways.

PubMed: 24814347
DOI: 10.1038/nsmb.2829

実験手法

SOLUTION NMR