| Structural highlights
Function
[CED9_CAEEL] Plays a major role in programmed cell death (PCD, apoptosis). Egl-1 binds to and directly inhibits the activity of ced-9, releasing the cell death activator ced-4 from a ced-9/ced-4 containing protein complex and allowing ced-4 to activate the cell-killing caspase ced-3.[1] [2] [3] [4] [5] [6] [EGL1_CAEEL] Plays a major role in programmed cell death (PCD or apoptosis) by negatively regulating ced-9. Binds to and directly inhibits the activity of ced-9, releasing the cell death activator ced-4 from a ced-9/ced-4 containing protein complex and allowing ced-4 to activate the cell-killing caspase ced-3.[7] [8] [9]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Programmed cell death in Caenorhabditis elegans is initiated by the binding of EGL-1 to CED-9, which disrupts the CED-4/CED-9 complex and allows CED-4 to activate the cell-killing caspase CED-3. Here we demonstrate that the C-terminal half of EGL-1 is necessary and sufficient for binding to CED-9 and for killing cells. Structure of the EGL-1/CED-9 complex revealed that EGL-1 adopts an extended alpha-helical conformation and induces substantial structural rearrangements in CED-9 upon binding. EGL-1 interface mutants failed to bind to CED-9 or to release CED-4 from the CED-4/CED-9 complex, and were unable to induce cell death in vivo. A surface patch on CED-9, different from that required for binding to EGL-1, was identified to be responsible for binding to CED-4. These data suggest a working mechanism for the release of CED-4 from the CED-4/CED-9 complex upon EGL-1 binding and provide a mechanistic framework for understanding apoptosis activation in C. elegans.
Structural, biochemical, and functional analyses of CED-9 recognition by the proapoptotic proteins EGL-1 and CED-4.,Yan N, Gu L, Kokel D, Chai J, Li W, Han A, Chen L, Xue D, Shi Y Mol Cell. 2004 Sep 24;15(6):999-1006. PMID:15383288[10]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Hengartner MO, Horvitz HR. C. elegans cell survival gene ced-9 encodes a functional homolog of the mammalian proto-oncogene bcl-2. Cell. 1994 Feb 25;76(4):665-76. PMID:7907274
- ↑ Spector MS, Desnoyers S, Hoeppner DJ, Hengartner MO. Interaction between the C. elegans cell-death regulators CED-9 and CED-4. Nature. 1997 Feb 13;385(6617):653-6. PMID:9024666 doi:http://dx.doi.org/10.1038/385653a0
- ↑ Wu D, Wallen HD, Nunez G. Interaction and regulation of subcellular localization of CED-4 by CED-9. Science. 1997 Feb 21;275(5303):1126-9. PMID:9027313
- ↑ Conradt B, Horvitz HR. The C. elegans protein EGL-1 is required for programmed cell death and interacts with the Bcl-2-like protein CED-9. Cell. 1998 May 15;93(4):519-29. PMID:9604928
- ↑ Chen F, Hersh BM, Conradt B, Zhou Z, Riemer D, Gruenbaum Y, Horvitz HR. Translocation of C. elegans CED-4 to nuclear membranes during programmed cell death. Science. 2000 Feb 25;287(5457):1485-9. PMID:10688797
- ↑ Yan N, Gu L, Kokel D, Chai J, Li W, Han A, Chen L, Xue D, Shi Y. Structural, biochemical, and functional analyses of CED-9 recognition by the proapoptotic proteins EGL-1 and CED-4. Mol Cell. 2004 Sep 24;15(6):999-1006. PMID:15383288 doi:10.1016/j.molcel.2004.08.022
- ↑ Conradt B, Horvitz HR. The C. elegans protein EGL-1 is required for programmed cell death and interacts with the Bcl-2-like protein CED-9. Cell. 1998 May 15;93(4):519-29. PMID:9604928
- ↑ Chen F, Hersh BM, Conradt B, Zhou Z, Riemer D, Gruenbaum Y, Horvitz HR. Translocation of C. elegans CED-4 to nuclear membranes during programmed cell death. Science. 2000 Feb 25;287(5457):1485-9. PMID:10688797
- ↑ Yan N, Gu L, Kokel D, Chai J, Li W, Han A, Chen L, Xue D, Shi Y. Structural, biochemical, and functional analyses of CED-9 recognition by the proapoptotic proteins EGL-1 and CED-4. Mol Cell. 2004 Sep 24;15(6):999-1006. PMID:15383288 doi:10.1016/j.molcel.2004.08.022
- ↑ Yan N, Gu L, Kokel D, Chai J, Li W, Han A, Chen L, Xue D, Shi Y. Structural, biochemical, and functional analyses of CED-9 recognition by the proapoptotic proteins EGL-1 and CED-4. Mol Cell. 2004 Sep 24;15(6):999-1006. PMID:15383288 doi:10.1016/j.molcel.2004.08.022
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