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.
journal_name
Nat Struct Mol Bioljournal_title
Nature structural & molecular biologyauthors
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 PEdoi
10.1038/s41594-020-0494-5subject
Has Abstractpub_date
2020-11-01 00:00:00pages
1024-1031issue
11eissn
1545-9993issn
1545-9985pii
10.1038/s41594-020-0494-5journal_volume
27pub_type
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