7K02

The crystal structure of a BAK dimer activated by detergent

7K02 の概要

• エントリーDOI: 10.2210/pdb7k02/pdb
• 関連するPDBエントリー: 4U2V
• 分子名称: Bcl-2 homologous antagonist/killer (1 entity in total)
• 機能のキーワード: bak, bh3-in-groove dimer, bcl-2 fold, pore forming, proapoptotic, apoptosis
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 81602.37

構造登録者

Birkinshaw, R.W.,Czabotar, P.E. (登録日: 2020-09-02, 公開日: 2021-03-31, 最終更新日: 2023-10-18)

主引用文献

Birkinshaw, R.W.,Iyer, S.,Lio, D.,Luo, C.S.,Brouwer, J.M.,Miller, M.S.,Robin, A.Y.,Uren, R.T.,Dewson, G.,Kluck, R.M.,Colman, P.M.,Czabotar, P.E.
Structure of detergent-activated BAK dimers derived from the inert monomer.
Mol.Cell, 81:2123-, 2021

PubMed Abstract: A body of data supports the existence of core (α2-α5) dimers of BAK and BAX in the oligomeric, membrane-perturbing conformation of these essential apoptotic effector molecules. Molecular structures for these dimers have only been captured for truncated constructs encompassing the core domain alone. Here, we report a crystal structure of BAK α2-α8 dimers (i.e., minus its flexible N-terminal helix and membrane-anchoring C-terminal segment) that has been obtained through the activation of monomeric BAK with the detergent C12E8. Core dimers are evident, linked through the crystal by contacts via latch (α6-α8) domains. This crystal structure shows activated BAK dimers with the extended latch domain present. Our data provide direct evidence for the conformational change converting BAK from inert monomer to the functional dimer that destroys mitochondrial integrity. This dimer is the smallest functional unit for recombinant BAK or BAX described so far.

PubMed: 33794146
DOI: 10.1016/j.molcel.2021.03.014

実験手法

X-RAY DIFFRACTION (3.4 Å)