Journal article
Dynamic reconfiguration of pro-apoptotic BAK on membranes
JJ Sandow, IKL Tan, AS Huang, S Masaldan, JP Bernardini, AZ Wardak, RW Birkinshaw, RL Ninnis, Z Liu, D Dalseno, D Lio, G Infusini, PE Czabotar, AI Webb, G Dewson
EMBO Journal | Published : 2021
Abstract
BAK and BAX, the effectors of intrinsic apoptosis, each undergo major reconfiguration to an activated conformer that self-associates to damage mitochondria and cause cell death. However, the dynamic structural mechanisms of this reconfiguration in the presence of a membrane have yet to be fully elucidated. To explore the metamorphosis of membrane-bound BAK, we employed hydrogen-deuterium exchange mass spectrometry (HDX-MS). The HDX-MS profile of BAK on liposomes comprising mitochondrial lipids was consistent with known solution structures of inactive BAK. Following activation, HDX-MS resolved major reconfigurations in BAK. Mutagenesis guided by our HDX-MS profiling revealed that the BCL-2 ho..
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Awarded by University of Melbourne
Funding Acknowledgements
The authors acknowledge Sweta Iyer, Ruth Kluck, Melissa Shi and Peter Colman for discussions and reagents. This research was supported by grants from the National Health and Medical Research Council Australia to PEC and GD (GNT1148174). DD and ASH are supported by Melbourne University Research Scholarships. GD is supported by a Fellowship from the Bodhi Education Fund. This work was supported by operational infrastructure grants through the Australian Government Independent Research Institute Infrastructure Support Scheme (9000587) and the Victorian State Government Operational Infrastructure Support, Australia.