Structure of the BAK-activating antibody 7D10 bound to BAK reveals an unexpected role for the α1-α2 loop in BAK activation.
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ABSTRACT:
SUBMITTER: Robin AY
PROVIDER: S-EPMC9433411 | biostudies-literature | 2022 Sep
REPOSITORIES: biostudies-literature
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Structure of the BAK-activating antibody 7D10 bound to BAK reveals an unexpected role for the α1-α2 loop in BAK activation.
Robin Adeline Y AY Miller Michelle S MS Iyer Sweta S Shi Melissa X MX Wardak Ahmad Z AZ Lio Daisy D Smith Nicholas A NA Smith Brian J BJ Birkinshaw Richard W RW Czabotar Peter E PE Kluck Ruth M RM Colman Peter M PM
Cell death and differentiation 20220312 9
Pro-apoptotic BAK and BAX are activated by BH3-only proteins to permeabilise the outer mitochondrial membrane. The antibody 7D10 also activates BAK on mitochondria and its epitope has previously been mapped to BAK residues in the loop connecting helices α1 and α2 of BAK. A crystal structure of the complex between the Fv fragment of 7D10 and the BAK mutant L100A suggests a possible mechanism of activation involving the α1-α2 loop residue M60. M60 mutants of BAK have reduced stability and elevated ...[more]
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