Journal article

Bak Activation for Apoptosis Involves Oligomerization of Dimers via Their alpha 6 Helices

Grant Dewson, Tobias Kratina, Peter Czabotar, Catherine L Day, Jerry M Adams, Ruth M Kluck

MOLECULAR CELL | CELL PRESS | Published : 2009

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 alpha6 helices. Cysteine residues placed in alpha6 could be crosslinked only after apoptotic signaling. Cysteines placed at both interfaces established that the BH3:groove dimer is symmetric and that the alpha6:alpha6 interface can link these dimers into homo-oligomers containing at least 18 Bak molecules. A putative zinc-binding site in a..

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Grants

Awarded by NHMRC


Funding Acknowledgements

We thank D. Huang, P. Colman, J. Gulbis, M. Hinds, J. Babon, J. Fletcher, A. Strasser, J.-G. Zhang, and P. Zalewski for discussions and critical comments on the manuscript and the flow cytometry facility and S. Coyne, G. Thompson, and S. Ma for technical assistance. The work was funded by The Cancer Council of Victoria, the NHMRC (Project Grant 575559 and Program Grant 461221), and the Australian Research Council.