Structure of detergent-activated BAK dimers derived from the inert monomer
Richard W Birkinshaw, Sweta Iyer, Daisy Lio, Cindy S Luo, Jason M Brouwer, Michelle S Miller, Adeline Y Robin, Rachel T Uren, Grant Dewson, Ruth M Kluck, Peter M Colman, Peter E Czabotar
Molecular Cell | CELL PRESS | Published : 2021
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 doma..View full abstract
Awarded by NHMRC
Awarded by Leukemia and Lymphoma Society
Research in the authors' laboratory is supported by NHMRC project grants (1059331 and 1079706), ideas grant (2001406), a program grant (1113133), fellowships (1116934 PMC, 1079700 PEC), and the Leukemia and Lymphoma Society (SCOR 7015-18). This research was undertaken in part using the MX2 beamline at the Australian Synchrotron, part of ANSTO, and made use of the Australian Cancer Research Foundation (ACRF) detector. We also thank Angus Cowan for providing bacterial expression plasmids with the BAKhis W125P and R137A mutations and Ahmad Wardak for preparing the liposomes used in our experiments.