Structure of detergent-activated BAK dimers derived from the inert monomer
Journal Title
Molecular Cell
Publication Type
epub ahead of print
A body of data supports the existence of core (α2-α5) dimers of BAK and BAX in the oligomeric, membrane-perturbing conformation of these essential apoptotic effector molecules. Molecular structures for these dimers have only been captured for truncated constructs encompassing the core domain alone. Here, we report a crystal structure of BAK α2-α8 dimers (i.e., minus its flexible N-terminal helix and membrane-anchoring C-terminal segment) that has been obtained through the activation of monomeric BAK with the detergent C12E8. Core dimers are evident, linked through the crystal by contacts via latch (α6-α8) domains. This crystal structure shows activated BAK dimers with the extended latch domain present. Our data provide direct evidence for the conformational change converting BAK from inert monomer to the functional dimer that destroys mitochondrial integrity. This dimer is the smallest functional unit for recombinant BAK or BAX described so far.
Cell Press
Apoptosis; Bak; BAK activation; BCL-2 family proteins; BH3-in-groove core dimers; Detergent mediated dimerization; X-ray crystallography; cytochrome c release; membrane rupture
WEHI Research Division(s)
Structural Biology; Blood Cells And Blood Cancer; Ubiquitin Signalling
PubMed ID
Rights Notice
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Creation Date: 2021-04-28 08:15:47
Last Modified: 2021-05-06 08:35:30
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