8CZH

Human BAK in complex with the dM2 peptide

8CZH の概要

• エントリーDOI: 10.2210/pdb8czh/pdb
• 分子名称: Bcl-2 homologous antagonist/killer, DM2 peptide (3 entities in total)
• 機能のキーワード: bak, activator, bcl-2 family, 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: 21735.43

構造登録者

Aguilar, F.,Keating, A.E. (登録日: 2022-05-24, 公開日: 2023-01-11, 最終更新日: 2024-10-09)

主引用文献

Aguilar, F.,Yu, S.,Grant, R.A.,Swanson, S.,Ghose, D.,Su, B.G.,Sarosiek, K.A.,Keating, A.E.
Peptides from human BNIP5 and PXT1 and non-native binders of pro-apoptotic BAK can directly activate or inhibit BAK-mediated membrane permeabilization.
Structure, 31:265-281.e7, 2023

PubMed Abstract: Apoptosis is important for development and tissue homeostasis, and its dysregulation can lead to diseases, including cancer. As an apoptotic effector, BAK undergoes conformational changes that promote mitochondrial outer membrane disruption, leading to cell death. This is termed "activation" and can be induced by peptides from the human proteins BID, BIM, and PUMA. To identify additional peptides that can regulate BAK, we used computational protein design, yeast surface display screening, and structure-based energy scoring to identify 10 diverse new binders. We discovered peptides from the human proteins BNIP5 and PXT1 and three non-native peptides that activate BAK in liposome assays and induce cytochrome c release from mitochondria. Crystal structures and binding studies reveal a high degree of similarity among peptide activators and inhibitors, ruling out a simple function-determining property. Our results shed light on the vast peptide sequence space that can regulate BAK function and will guide the design of BAK-modulating tools and therapeutics.

PubMed: 36706751
DOI: 10.1016/j.str.2023.01.001

実験手法

X-RAY DIFFRACTION (1.3 Å)