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SUMMARY:Structural Insights into Bak Activation and Oligomerisation
DTSTART;VALUE=DATE-TIME:20141120T003000Z
DTEND;VALUE=DATE-TIME:20141120T005000Z
DTSTAMP;VALUE=DATE-TIME:20260711T060259Z
UID:indico-contribution-698@events01.synchrotron.org.au
DESCRIPTION:Speakers: Jason Brouwer (Walter and Eliza Hall Institute of Me
 dical Research)\nApoptotic stimuli activate and oligomerise the pro-apopto
 tic proteins Bak and Bax resulting in mitochondrial outer membrane permeab
 ilisation and subsequent cell death. Crystal structures by Czabotar et al.
  (2013) provided novel insights into BH3-only induced Bax activation and o
 ligomerisation\, namely the separation of the core and latch domains\, fol
 lowed by core domain dimerisation. Here we provide complementary studies o
 n the related protein Bak. We present the crystal structures of Bak core-l
 atch domain swapped dimers and demonstrate their dissociation upon Bak act
 ivation. A second crystal structure of the Bak core domain provides the fi
 rst high-resolution details for this key dimerisation unit upon which the 
 larger Bak oligomer builds. Cellular assays\, guided by the presented crys
 tal structures\, confirm the physiological relevance of these key events i
 n the intrinsic apoptotic pathway (Brouwer et al. 2014). These studies con
 firmed an analogous mechanism for activation and dimerization of Bak and B
 ax in response to BH3-only peptides. More recently we have performed struc
 tural studies on the direct interaction of BH3-only peptides with Bak. We 
 have gained insight into the differences between interactions of BH3 only 
 proteins with Bak compared to the pro-survival proteins\; this may inform 
 the design of novel therapeutics to manipulate cell death.\n\nReferences\n
 \nBrouwer et al. (2014)\, Mol Cell\, published online 28th August\, http:/
 /dx.doi.org/10.1016/j.molcel.2014.07.016\n\nCzabotar et al. (2013)\, Cell 
 152(3): 519-531.\n\nhttps://events01.synchrotron.org.au/event/3/contributi
 ons/698/
LOCATION: Oliphant Auditorium
URL:https://events01.synchrotron.org.au/event/3/contributions/698/
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