4ZIF

Crystal Structure of core/latch dimer of Bax in complex with BimBH3mini

4ZIF の概要

• エントリーDOI: 10.2210/pdb4zif/pdb
• 関連するPDBエントリー: 4ZIE 4ZIG 4ZIH 4ZII
• 分子名称: Apoptosis regulator BAX, Bcl-2-like protein 11 (3 entities in total)
• 機能のキーワード: bax, apoptosis, bh3 domain, structural genomics, the walter and eliza hall institute of medical research
• 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: 21003.80

構造登録者

Robin, A.Y.,Krishna Kumar, K.,Westphal, D.,Wardak, A.Z.,Thompson, G.V.,Dewson, G.,Colman, P.M.,Czabotar, P.E. (登録日: 2015-04-28, 公開日: 2015-07-22, 最終更新日: 2023-09-27)

主引用文献

Robin, A.Y.,Krishna Kumar, K.,Westphal, D.,Wardak, A.Z.,Thompson, G.V.,Dewson, G.,Colman, P.M.,Czabotar, P.E.
Crystal structure of Bax bound to the BH3 peptide of Bim identifies important contacts for interaction.
Cell Death Dis, 6:e1809-e1809, 2015

PubMed Abstract: The BH3-only protein Bim is a potent direct activator of the proapoptotic effector protein Bax, but the structural basis for its activity has remained poorly defined. Here we describe the crystal structure of the BimBH3 peptide bound to BaxΔC26 and structure-based mutagenesis studies. Similar to BidBH3, the BimBH3 peptide binds into the cognate surface groove of Bax using the conserved hydrophobic BH3 residues h1-h4. However, the structure and mutagenesis data show that Bim is less reliant compared with Bid on its 'h0' residues for activating Bax and that a single amino-acid difference between Bim and Bid encodes a fivefold difference in Bax-binding potency. Similar to the structures of BidBH3 and BaxBH3 bound to BaxΔC21, the structure of the BimBH3 complex with BaxΔC displays a cavity surrounded by Bax α1, α2, α5 and α8. Our results are consistent with a model in which binding of an activator BH3 domain to the Bax groove initiates separation of its core (α2-α5) and latch (α6-α8) domains, enabling its subsequent dimerisation and the permeabilisation of the mitochondrial outer membrane.

PubMed: 26158515
DOI: 10.1038/cddis.2015.141

実験手法

X-RAY DIFFRACTION (2.401 Å)