A Stapled BID BH3 Helix Directly Binds and Activates BAX
| Autor: | Joel Morash, Jill K. Fisher, Kyoung Joon Oh, Loren D. Walensky, Scott Barbuto, Stanley J. Korsmeyer, Eric E. Smith, Kenneth L. Pitter, Gregory L. Verdine |
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| Rok vydání: | 2006 |
| Předmět: |
Molecular Sequence Data
bcl-X Protein Apoptosis Plasma protein binding Biology Mitochondrion Jurkat cells 03 medical and health sciences Jurkat Cells 0302 clinical medicine Humans Amino Acid Sequence Peptide sequence Molecular Biology 030304 developmental biology bcl-2-Associated X Protein 0303 health sciences Dose-Response Relationship Drug Sequence Homology Amino Acid Cell Membrane Cell Biology Cell cycle Transport protein Cell biology Cytosol Protein Transport Biochemistry 030220 oncology & carcinogenesis Liposomes biological phenomena cell phenomena and immunity Peptides BH3 Interacting Domain Death Agonist Protein Protein Binding |
| Zdroj: | Molecular Cell. 24(2):199-210 |
| ISSN: | 1097-2765 |
| DOI: | 10.1016/j.molcel.2006.08.020 |
| Popis: | BAX is a multidomain proapoptotic BCL-2 family protein that resides in the cytosol until activated by an incompletely understood trigger mechanism, which facilitates BAX translocation to mitochondria and downstream death events. Whether BAX is activated by direct contact with select BH3-only members of the BCL-2 family is highly debated. Here we detect and quantify a direct binding interaction between BAX and a hydrocarbon-stapled BID BH3 domain, which triggers the functional activation of BAX at nanomolar doses in vitro. Chemical reinforcement of BID BH3 alpha helicity was required to reveal the direct BID BH3-BAX association. We confirm the specificity of this BH3 interaction by characterizing a stapled BAD BH3 peptide that interacts with antiapoptotic BCL-X(L) but does not bind or activate BAX. We further demonstrate that membrane targeting of stapled BID BH3 optimizes its ability to activate BAX, supporting a model in which BID directly engages BAX to trigger mitochondrial apoptosis. |
| Databáze: | OpenAIRE |
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