Bak core and latch domains separate during activation, and freed core domains form symmetric homodimers
Details
Publication Year 2014-08-27, Volume 55, Issue #6, Page 938-46
Journal Title
Mol Cell
Publication Type
Journal Article
Abstract
Apoptotic stimuli activate and oligomerize the proapoptotic proteins Bak and Bax, resulting in mitochondrial outer-membrane permeabilization and subsequent cell death. This activation can occur when certain BH3-only proteins interact directly with Bak and Bax. Recently published crystal structures reveal that Bax separates into core and latch domains in response to BH3 peptides. The distinguishing characteristics of BH3 peptides capable of directly activating Bax were also elucidated. Here we identify specific BH3 peptides capable of "unlatching" Bak and describe structural insights into Bak activation and oligomerization. Crystal structures and crosslinking experiments demonstrate that Bak undergoes a conformational change similar to that of Bax upon activation. A structure of the Bak core domain dimer provides a high-resolution image of this key intermediate in the pore-forming oligomer. Our results confirm an analogous mechanism for activation and dimerization of Bak and Bax in response to certain BH3 peptides.
Publisher
Cell Press
WEHI Research Division(s)
Cell Signalling And Cell Death; Structural Biology; Molecular Genetics Of Cancer
Rights Notice
Copyright © 2014 Elsevier B.V. except certain content provided by third parties. ScienceDirect® is a registered trademark of Elsevier B.V.


Creation Date: 2014-09-12 02:01:39
Last Modified: 0001-01-01 12:00:00
An error has occurred. This application may no longer respond until reloaded. Reload 🗙