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          Institute: MPI für Entwicklungsbiologie     Collection: Abteilung 1 - Protein Evolution (A. Lupas)     Display Documents

ID: 460640.0, MPI für Entwicklungsbiologie / Abteilung 1 - Protein Evolution (A. Lupas)
Molecular details of Bax activation, oligomerization and membrane insertion
Authors:Bleicken, S.; Classen, M.; Padmavathi, P. V.; Ishikawa, T.; Zeth, K.; Steinhoff, H. J.; Bordignon, E.
Date of Publication (YYYY-MM-DD):2009-12-13
Title of Journal:J Biol Chem
Start Page:6636
End Page:6647
Review Status:not specified
Audience:Not Specified
Abstract / Description:Bax and Bid are pro-apoptotic members of the Bcl-2 protein family. Upon cleavage by caspase 8, Bid activates Bax. Activated Bax inserts into the mitochondrial outer membrane, forming oligomers which lead to membrane poration, release of cytochrome c and apoptosis. The detailed mechanism of Bax activation and the topology and composition of the oligomers are still under debate. Here molecular details of Bax activation and oligomerization were obtained by application of several biophysical techniques, including AFM, cryo-EM and particularly electron paramagnetic resonance (EPR) spectroscopy performed on spin labeled Bax. Incubation with detergents, reconstitution or Bid-triggered insertion into liposomes were found to be effective in inducing Bax oligomerization. Bid was shown to activate Bax independently of the stoichiometric ratio, suggesting that Bid has a catalytic function and the interaction with Bax is transient. The formation of a stable dimerization interface involving two BH3 domains was found to be the nucleation event for Bax homo-oligomerization. Based on inter-molecular distance determined by EPR, a model of six adjacent Bax molecules in the oligomer is presented where the hydrophobic hairpins (helices alpha5 and alpha6) are equally spaced in the membrane and the two BH3 domains are in close vicinity in the dimer interface, separated by > 5 nm from the next BH3 pairs.
External Publication Status:published
Document Type:Article
Affiliations:MPI für Entwicklungsbiologie/Abteilung 1 - Proteinevolution (Andrei Lupas)
External Affiliations:%G Eng
Identifiers:ISSN:1083-351X (Electronic) 0021-9258 (Linking) %R M109... [ID No:1]
URL: [ID No:2]
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