5FMK

Bcl-xL with Bak BH3 complex

5FMK の概要

• エントリーDOI: 10.2210/pdb5fmk/pdb
• 関連するPDBエントリー: 5FMI 5FMJ
• 分子名称: BCL-XL, BCL-2 HOMOLOGOUS ANTAGONIST/KILLER, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: bcl-xl, bak, bh3 domain, apoptosis, bcl-2 family
• 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; Mitochondrion membrane ; Single-pass membrane protein : Q16611
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 22143.65

構造登録者

Fairlie, W.D.,Lee, E.F.,Smith, B.J.,Czabotar, P.E.,Colman, P.M. (登録日: 2015-11-06, 公開日: 2016-06-01, 最終更新日: 2024-01-10)

主引用文献

Lee, E.F.,Grabow, S.,Chappaz, S.,Dewson, G.,Hockings, C.,Kluck, R.M.,Gray, D.H.,Witkowski, M.T.,Evangelista, M.,Pettikiriarachchi, A.,Bouillet, P.,Lane, R.M.,Czabotar, P.E.,Colman, P.M.,Smith, B.J.,Kile, B.T.,Fairlie, W.D.
Physiological Restraint of Bak by Bcl-Xl is Essential for Cell Survival.
Genes Dev., 30:1240-, 2016

PubMed Abstract: Due to the myriad interactions between prosurvival and proapoptotic members of the Bcl-2 family of proteins, establishing the mechanisms that regulate the intrinsic apoptotic pathway has proven challenging. Mechanistic insights have primarily been gleaned from in vitro studies because genetic approaches in mammals that produce unambiguous data are difficult to design. Here we describe a mutation in mouse and human Bak that specifically disrupts its interaction with the prosurvival protein Bcl-xL Substitution of Glu75 in mBak (hBAK Q77) for leucine does not affect the three-dimensional structure of Bak or killing activity but reduces its affinity for Bcl-xL via loss of a single hydrogen bond. Using this mutant, we investigated the requirement for physical restraint of Bak by Bcl-xL in apoptotic regulation. In vitro, Bak(Q75L) cells were significantly more sensitive to various apoptotic stimuli. In vivo, loss of Bcl-xL binding to Bak led to significant defects in T-cell and blood platelet survival. Thus, we provide the first definitive in vivo evidence that prosurvival proteins maintain cellular viability by interacting with and inhibiting Bak.

PubMed: 27198225
DOI: 10.1101/GAD.279414.116

実験手法

X-RAY DIFFRACTION (1.731 Å)