Bak Activation for Apoptosis Involves Oligomerization of Dimers via Their alpha 6 Helices
- Author(s)
- Dewson, G; Kratina, T; Czabotar, P; Day, CL; Adams, JM; Kluck, RM;
- Details
- Publication Year 2009-11-25,Volume 36,Issue #4,Page 696-703
- Journal Title
- MOLECULAR CELL
- Publication Type
- Journal Article
- Abstract
- A pivotal step toward apoptosis is oligomerization of the Bcl-2 relative Bak. We recently reported that its oligomerization initiates by insertion of an exposed BH3 domain into the groove of another Bak monomer. We now report that the resulting BH3:groove dimers can be converted to the larger oligomers that permeabilize mitochondria by an interface between alpha 6 helices. Cysteine residues placed in alpha 6 could be crosslinked only after apoptotic signaling. Cysteines placed at both interfaces established that the BH3:groove dimer is symmetric and that the alpha 6:alpha 6 interface can link these dimers into homo-oligomers, containing at least 18 Bak molecules. A putative zinc-binding site in alpha 6 was not required to form the alpha 6:alpha 6 interface, and its mutation in full-length Bak did not affect Bak conformation, oligomerization, or function. We conclude that alpha 6:alpha 6 interaction occurs during Bak oligomerization and proapoptotic function, but we find no evidence that zinc binding to that interface regulates apoptosis.
- Publisher
- CELL PRESS
- Keywords
- BH3-ONLY PROTEINS; CYTOCHROME-C; BH3 DOMAINS; BCL-2; DEATH; PERMEABILIZATION; MITOCHONDRIA; SITE
- Publisher's Version
- https://doi.org/10.1016/j.molcel.2009.11.008
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2009-11-25 12:00:00