Bcl-XL mutations suppress cellular sensitivity to antimycin A
| Autor: | Kam Y.Z. Zhang, Chris D. Giedt, Jason W. O'Neill, Kristine M. Kim, Michael Keoni Manion, David M. Hockenbery |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Protein Folding
Cell Survival Mutant Molecular Sequence Data bcl-X Protein Antimycin A Bcl-xL Biochemistry chemistry.chemical_compound Point Mutation Amino Acid Sequence Binding site Cytotoxicity Molecular Biology Binding Sites biology Cell Biology Molecular biology In vitro Cell biology Dissociation constant chemistry Proto-Oncogene Proteins c-bcl-2 Apoptosis biology.protein Hydrophobic and Hydrophilic Interactions |
| Zdroj: | The Journal of biological chemistry. 279(3) |
| ISSN: | 0021-9258 |
| Popis: | Cells expressing high levels of the BCL-X(L) anti-apoptotic protein are preferentially killed by the mitochondrial inhibitor antimycin A (AA). Computational modeling predicts a binding site for AA in the extended hydrophobic groove on BCL-X(L), previously identified as an interface for dimerization to BAX and related proapoptotic proteins. Here, we identify BCL-X(L) hydrophobic groove mutants with normal cellular anti-apoptotic function but suppressed sensitivity to AA. The LD(50) of AA for cells expressing BCL-X(L) mutants directly correlates with the measured in vitro dissociation constants for AA binding. These results indicate that BCL-X(L) is a principal target mediating AA cytotoxicity. |
| Databáze: | OpenAIRE |
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