7k02
The crystal structure of a BAK dimer activated by detergent
Structural highlights
FunctionBAK_HUMAN In the presence of an appropriate stimulus, accelerates programmed cell death by binding to, and antagonizing the anti-apoptotic action of BCL2 or its adenovirus homolog E1B 19k protein. Low micromolar levels of zinc ions inhibit the promotion of apoptosis.[1] [2] Publication Abstract from PubMedA body of data supports the existence of core (alpha2-alpha5) 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 alpha2-alpha8 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 (alpha6-alpha8) 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. Structure of detergent-activated BAK dimers derived from the inert monomer.,Birkinshaw RW, Iyer S, Lio D, Luo CS, Brouwer JM, Miller MS, Robin AY, Uren RT, Dewson G, Kluck RM, Colman PM, Czabotar PE Mol Cell. 2021 Mar 23. pii: S1097-2765(21)00182-9. doi:, 10.1016/j.molcel.2021.03.014. PMID:33794146[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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