4QVF

Crystal structure of Bcl-xL in complex with BIM BH3 domain

4QVF の概要

• エントリーDOI: 10.2210/pdb4qvf/pdb
• 関連するPDBエントリー: 1MAZ 4QVE
• 分子名称: Bcl-2-like protein 1, Peptide from Bcl-2-like protein 11 (3 entities in total)
• 機能のキーワード: protein-peptide complex, bcl-2 like, heterodimer, apoptosis, anti-apoptotic, bh3 binding, bim bh3
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Isoform Bcl-X(L): Mitochondrion inner membrane : Q07817; Endomembrane system ; Peripheral membrane protein . 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: 22587.91

構造登録者

Sreekanth, R.,Yoon, H.S. (登録日: 2014-07-15, 公開日: 2015-06-10, 最終更新日: 2023-11-08)

主引用文献

Rajan, S.,Choi, M.,Baek, K.,Yoon, H.S.
Bh3 induced conformational changes in Bcl-Xl revealed by crystal structure and comparative analysis.
Proteins, 83:1262-1272, 2015

PubMed Abstract: Apoptosis or programmed cell death is a regulatory process in cells in response to stimuli perturbing physiological conditions. The Bcl-2 family of proteins plays an important role in regulating homeostasis during apoptosis. In the process, the molecular interactions among the three members of this family, the pro-apoptotic, anti-apoptotic and BH3-only proteins at the mitochondrial outer membrane define the fate of a cell. Here, we report the crystal structures of the human anti-apoptotic protein Bcl-XL in complex with BH3-only BID(BH3) and BIM(BH3) peptides determined at 2.0 Å and 1.5 Å resolution, respectively. The BH3 peptides bind to the canonical hydrophobic pocket in Bcl-XL and adopt an alpha helical conformation in the bound form. Despite a similar structural fold, a comparison with other BH3 complexes revealed structural differences due to their sequence variations. In the Bcl-XL-BID(BH3) complex we observed a large pocket, in comparison with other BH3 complexes, lined by residues from helices α1, α2, α3, and α5 located adjacent to the canonical hydrophobic pocket. These results suggest that there are differences in the mode of interactions by the BH3 peptides that may translate into functional differences in apoptotic regulation.

PubMed: 25907960
DOI: 10.1002/prot.24816

実験手法

X-RAY DIFFRACTION (1.531 Å)