6UXM

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

Summary for 6UXM

• Entry DOI: 10.2210/pdb6uxm/pdb
• Descriptor: Bcl-2 homologous antagonist/killer, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (2 entities in total)
• Functional Keywords: pore-forming protein, apoptosis
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 6
• Total formula weight: 61468.33

Authors

Cowan, A.D.,Colman, P.M.,Czabotar, P.E. (deposition date: 2019-11-07, release date: 2020-09-02, Last modification date: 2023-10-11)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.49 Å)