6UXM

Crystal structure of BAK core domain BH3-groove-dimer in complex with E. coli lipid

6UXM の概要

• エントリーDOI: 10.2210/pdb6uxm/pdb
• 分子名称: Bcl-2 homologous antagonist/killer, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (2 entities in total)
• 機能のキーワード: pore-forming protein, 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: 61468.33

構造登録者

Cowan, A.D.,Colman, P.M.,Czabotar, P.E. (登録日: 2019-11-07, 公開日: 2020-09-02, 最終更新日: 2023-10-11)

主引用文献

Cowan, A.D.,Smith, N.A.,Sandow, J.J.,Kapp, E.A.,Rustam, Y.H.,Murphy, J.M.,Brouwer, J.M.,Bernardini, J.P.,Roy, M.J.,Wardak, A.Z.,Tan, I.K.,Webb, A.I.,Gulbis, J.M.,Smith, B.J.,Reid, G.E.,Dewson, G.,Colman, P.M.,Czabotar, P.E.
BAK core dimers bind lipids and can be bridged by them.
Nat.Struct.Mol.Biol., 27:1024-1031, 2020

PubMed Abstract: BAK and BAX are essential mediators of apoptosis that oligomerize in response to death cues, thereby causing permeabilization of the mitochondrial outer membrane. Their transition from quiescent monomers to pore-forming oligomers involves a well-characterized symmetric dimer intermediate. However, no essential secondary interface that can be disrupted by mutagenesis has been identified. Here we describe crystal structures of human BAK core domain (α2-α5) dimers that reveal preferred binding sites for membrane lipids and detergents. The phospholipid headgroup and one acyl chain (sn2) associate with one core dimer while the other acyl chain (sn1) associates with a neighboring core dimer, suggesting a mechanism by which lipids contribute to the oligomerization of BAK. Our data support a model in which, unlike for other pore-forming proteins whose monomers assemble into oligomers primarily through protein-protein interfaces, the membrane itself plays a role in BAK and BAX oligomerization.

PubMed: 32929280
DOI: 10.1038/s41594-020-0494-5

実験手法

X-RAY DIFFRACTION (2.49 Å)