Journal article

Bak apoptotic pores involve a flexible C-terminal region and juxtaposition of the C-terminal transmembrane domains

S Iyer, F Bell, D Westphal, K Anwari, J Gulbis, BJ Smith, G Dewson, RM Kluck

CELL DEATH AND DIFFERENTIATION | NATURE PUBLISHING GROUP | Published : 2015

Abstract

Bak and Bax mediate apoptotic cell death by oligomerizing and forming a pore in the mitochondrial outer membrane. Both proteins anchor to the outer membrane via a C-terminal transmembrane domain, although its topology within the apoptotic pore is not known. Cysteine-scanning mutagenesis and hydrophilic labeling confirmed that in healthy mitochondria the Bak α9 segment traverses the outer membrane, with 11 central residues shielded from labeling. After pore formation those residues remained shielded, indicating that α9 does not line a pore. Bak (and Bax) activation allowed linkage of α9 to neighboring α9 segments, identifying an α9:α9 interface in Bak (and Bax) oligomers. Although the linkage..

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Grants

Awarded by NHMRC


Funding Acknowledgements

We thank Peter Colman and Rachel Uren for critical comments on the manuscript. We also thank Matthew Call and Melissa Call for advice on generating the C terminus swap mutants, Peter Czabotar for useful discussions, Ray Bartolo and Stephanie Fennell for technical support. GD and RMK acknowledge ARC Future Fellowships. Our work is supported by NHMRC grants (637337 and 1016701), and the Victorian State Government Operational Infrastructure Support and the Australian Government NHMRC IRIISS.