A Structural Viral Mimic of Prosurvival Bcl-2: A Pivotal Role for Sequestering Proapoptotic Bax and Bak
Many viruses express antiapoptotic proteins to counter host defense mechanisms that would otherwise trigger the rapid clearance of infected cells. For example, adenoviruses and some γ-herpesviruses express homologs of prosurvival Bcl-2 to subvert the host's apoptotic machinery. Myxoma virus, a...
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| Veröffentlicht in: | Molecular cell 2007-03, Vol.25 (6), p.933-942 |
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| creator | Kvansakul, Marc van Delft, Mark F. Lee, Erinna F. Gulbis, Jacqueline M. Fairlie, W. Douglas Huang, David C.S. Colman, Peter M. |
| description | Many viruses express antiapoptotic proteins to counter host defense mechanisms that would otherwise trigger the rapid clearance of infected cells. For example, adenoviruses and some γ-herpesviruses express homologs of prosurvival Bcl-2 to subvert the host's apoptotic machinery. Myxoma virus, a double-stranded DNA virus of the pox family, harbors antiapoptotic M11L, its virulence factor. Analysis of its three-dimensional structure reveals that despite lacking any primary sequence similarity to Bcl-2, it adopts a virtually identical protein fold. This allows it to associate with BH3 domains, especially those of Bax and Bak. We found that M11L acts primarily by sequestering Bax and Bak, thereby blocking the killing action of these essential cell-death mediators. These findings expand the family of protein sequences that act like Bcl-2 to block apoptosis and support the conclusion that the prosurvival action of these proteins critically depends on their ability to bind and antagonize Bax and/or Bak. |
| doi_str_mv | 10.1016/j.molcel.2007.02.004 |
| format | Article |
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We found that M11L acts primarily by sequestering Bax and Bak, thereby blocking the killing action of these essential cell-death mediators. 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| source | MEDLINE; Cell Press Free Archives; Elsevier ScienceDirect Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Free Full-Text Journals in Chemistry |
| subjects | Amino Acid Sequence APOPTOSIS BASIC BIOLOGICAL SCIENCES bcl-2 Homologous Antagonist-Killer Protein - chemistry bcl-2 Homologous Antagonist-Killer Protein - metabolism bcl-2-Associated X Protein - chemistry bcl-2-Associated X Protein - metabolism Cell Death CELLCYCLE CLEARANCE DNA MICROBIO Models, Molecular Molecular Sequence Data Myxoma virus - metabolism national synchrotron light source Protein Conformation Protein Folding PROTEINS Proto-Oncogene Proteins c-bcl-2 - chemistry Proto-Oncogene Proteins c-bcl-2 - metabolism Viral Proteins - chemistry Viral Proteins - metabolism VIRULENCE VIRUSES |
| title | A Structural Viral Mimic of Prosurvival Bcl-2: A Pivotal Role for Sequestering Proapoptotic Bax and Bak |
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