8IGC

Crystal structure of Bak bound to Bnip5 BH3

8IGC の概要

• エントリーDOI: 10.2210/pdb8igc/pdb
• 分子名称: Bcl-2 homologous antagonist/killer, Protein BNIP5 (3 entities in total)
• 機能のキーワード: bcl-2-interacting protein 5, bnip5, bak, bh3, 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: 21545.17

構造登録者

Ku, B.,Lim, D. (登録日: 2023-02-20, 公開日: 2023-09-20, 最終更新日: 2023-12-27)

主引用文献

Lim, D.,Jeong, D.E.,Shin, H.C.,Choi, J.S.,Seo, J.,Kim, S.J.,Ku, B.
Crystal structure of Bak bound to the BH3 domain of Bnip5, a noncanonical BH3 domain-containing protein.
Proteins, 92:44-51, 2024

PubMed Abstract: The activation or inactivation of B-cell lymphoma-2 (Bcl-2) antagonist/killer (Bak) is critical for controlling mitochondrial outer membrane permeabilization-dependent apoptosis. Its pro-apoptotic activity is controlled by intermolecular interactions with the Bcl-2 homology 3 (BH3) domain, which is accommodated in the hydrophobic pocket of Bak. Bcl-2-interacting protein 5 (Bnip5) is a noncanonical BH3 domain-containing protein that interacts with Bak. Bnip5 is characterized by its controversial effects on the regulation of the pro-apoptotic activity of Bak. In the present study, we determined the crystal structure of Bak bound to Bnip5 BH3. The intermolecular association appeared to be typical at first glance, but we found that it is maintained by tight hydrophobic interactions together with hydrogen/ionic bonds, which accounts for their high binding affinity with a dissociation constant of 775 nM. Structural analysis of the complex showed that Bnip5 interacts with Bak in a manner similar to that of the Bak-activating pro-apoptotic factor peroxisomal testis-enriched protein 1, particularly in the destabilization of the intramolecular electrostatic network of Bak. Our structure is considered to reflect the initial point of drastic and consecutive conformational and stoichiometric changes in Bak induced by Bnip5 BH3, which helps in explaining the effects of Bnip5 in regulating Bak-mediated apoptosis.

PubMed: 37553948
DOI: 10.1002/prot.26568

実験手法

X-RAY DIFFRACTION (1.697 Å)