Journal
MOLECULAR CELL
Volume 15, Issue 6, Pages 999-1006Publisher
CELL PRESS
DOI: 10.1016/j.molcel.2004.08.022
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Funding
- NIAID NIH HHS [R21 AI049905] Funding Source: Medline
- NIGMS NIH HHS [R01 GM064642] Funding Source: Medline
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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 QED-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. elegrans.
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