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Direct BAKtivation

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BAK is a proapoptotic BCL-2–family protein that resides in the mitochondrial outer membrane and transforms into a toxic oligomeric pore in response to overwhelming cellular stress. Biochemical and structural analyses of hydrocarbon-stapled signaling peptides in complex with BAK establish a direct mechanism for BAK activation.

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Figure 1: Two circuits were proposed for the protein interaction mechanisms by which BCL-2–family members regulate mitochondrial apoptosis.
Figure 2: The functional BH3-binding interfaces of BCL-2–family proteins.

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Acknowledgements

E.D. Smith is acknowledged for assistance with figure preparation.

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Correspondence to Loren D. Walensky.

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L.D.W. is a scientific advisory board member and consultant for Aileron Therapeutics.

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Walensky, L. Direct BAKtivation. Nat Struct Mol Biol 20, 536–538 (2013). https://doi.org/10.1038/nsmb.2579

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