BAK core dimers bind lipids and can be bridged by them
- Cowan, AD; Smith, NA; Sandow, JJ; Kapp, EA; Rustam, YH; Murphy, JM; Brouwer, JM; Bernardini, JP; Roy, MJ; Wardak, AZ; Tan, IK; Webb, AI; Gulbis, JM; Smith, BJ; Reid, GE; Dewson, G; Colman, PM; Czabotar, PE;
- Journal Title
- Nature Structural & Molecular Biology
- Publication Type
- Journal epub ahead of print
- 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 (alpha2-alpha5) 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.
- WEHI Research Division(s)
- Chemical Biology; Ubiquitin Signalling; Inflammation; Advanced Technology And Biology; Structural Biology
- PubMed ID
- Publisher's Version
- Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2020-10-02 10:28:04Last Modified: 2020-10-02 10:44:05