Structure of detergent-activated BAK dimers derived from the inert monomer
| Autor: | Peter M. Colman, Jason M. Brouwer, Grant Dewson, Cindy S. Luo, Richard W Birkinshaw, Ruth M. Kluck, Sweta Iyer, Michelle S. Miller, Adeline Y. Robin, Rachel T Uren, Peter E. Czabotar, Daisy Lio |
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| Rok vydání: | 2021 |
| Předmět: |
Models
Molecular Conformational change Dimer Detergents Crystal structure Biology Protein Structure Secondary 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Protein structure Animals Molecule Amino Acid Sequence Molecular Biology 030304 developmental biology Mice Knockout 0303 health sciences Cell Biology Mice Inbred C57BL Crystallography bcl-2 Homologous Antagonist-Killer Protein Monomer chemistry Liposomes Helix Protein Multimerization biological phenomena cell phenomena and immunity 030217 neurology & neurosurgery Bcl-2 Homologous Antagonist-Killer Protein |
| Zdroj: | Molecular Cell. 81:2123-2134.e5 |
| ISSN: | 1097-2765 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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