Document Detail


Bax dimerizes via a symmetric BH3:groove interface during apoptosis.
MedLine Citation:
PMID:  22015607     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
During apoptotic cell death, Bax and Bak change conformation and homo-oligomerize to permeabilize mitochondria. We recently reported that Bak homodimerizes via an interaction between the BH3 domain and hydrophobic surface groove, that this BH3:groove interaction is symmetric, and that symmetric dimers can be linked via the α6-helices to form the high order oligomers thought responsible for pore formation. We now show that Bax also dimerizes via a BH3:groove interaction after apoptotic signaling in cells and in mitochondrial fractions. BH3:groove dimers of Bax were symmetric as dimers but not higher order oligomers could be linked by cysteine residues placed in both the BH3 and groove. The BH3:groove interaction was evident in the majority of mitochondrial Bax after apoptotic signaling, and correlated strongly with cytochrome c release, supporting its central role in Bax function. A second interface between the Bax α6-helices was implicated by cysteine linkage studies, and could link dimers to higher order oligomers. We also found that a population of Bax:Bak heterodimers generated during apoptosis formed via a BH3:groove interaction, further demonstrating that Bax and Bak oligomerize via similar mechanisms. These findings highlight the importance of BH3:groove interactions in apoptosis regulation by the Bcl-2 protein family.Cell Death and Differentiation advance online publication, 21 October 2011; doi:10.1038/cdd.2011.138.
Authors:
G Dewson; S Ma; P Frederick; C Hockings; I Tan; T Kratina; R M Kluck
Related Documents :
20956147 - Pharmacological actions of statins: potential utility in copd.
17548647 - Cd8+ t cells are required for inflammation and destruction in cigarette smoke-induced e...
19386787 - Cystic fibrosis transmembrane conductance regulator and caveolin-1 regulate epithelial ...
15611267 - Morphine impairs host innate immune response and increases susceptibility to streptococ...
20956857 - Role of various cytokines and growth factors in pubertal development.
15972697 - Novel protein and poxvirus-based vaccine combinations for simultaneous induction of hum...
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-10-21
Journal Detail:
Title:  Cell death and differentiation     Volume:  -     ISSN:  1476-5403     ISO Abbreviation:  -     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-10-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9437445     Medline TA:  Cell Death Differ     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
1] The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia [2] Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Genetically defining the mechanism of Puma- and Bim-induced apoptosis.
Next Document:  SCaMC-1 promotes cancer cell survival by desensitizing mitochondrial permeability transition via ATP...