Journal article
The Bak core dimer focuses triacylglycerides in the membrane
NA Smith, AZ Wardak, AD Cowan, PM Colman, PE Czabotar, BJ Smith
Biophysical Journal | Published : 2022
Abstract
Apoptosis, the intrinsic programmed cell death process, is mediated by the Bcl-2 family members Bak and Bax. Activation via formation of symmetric core dimers and oligomerization on the mitochondrial outer membrane (MOM) leads to permeabilization and cell death. Although this process is linked to the MOM, the role of the membrane in facilitating such pores is poorly understood. We recently described Bak core domain dimers, revealing lipid binding sites and an initial role of lipids in oligomerization. Here we describe simulations that identified localized clustering and interaction of triacylglycerides (TAGs) with a minimized Bak dimer construct. Coalescence of TAGs occurred beneath this Bak..
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Awarded by National Health and Medical Research Council
Funding Acknowledgements
We acknowledge receipt of an Australian Postgraduate Award (to A.D.C.) and National Health and Medical Research Council fellowships 1079700 and 1116934 (to P.E.C. and P.M.C., respectively) . This work is supported by NHMRC project grant 1079706, Ideas grant 2001406, and Program grant 1113133 (to P.E.C. and P.M.C.) . Part of this work was undertaken us-ing resources from the National Computational Infrastructure, which is sup-ported by the Australian government and provided through Intersect Australia under LIEF grant LE170100032 and through the HPC-GPGPU Facility, which was established with the assistance of LIEF grant LE170100200.