Structural, biochemical, and functional analyses of CED-9 recognition by the proapoptotic proteins EGL-1 and CED-4

Nieng Yan, Lichuan Gu, David Kokel, Jijie Chai, Wenyu Li, Aidong Han, Lin Chen, Ding Xue, Yigong Shi

Research output: Contribution to journalArticle

82 Scopus citations

Abstract

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 α-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.

Original languageEnglish (US)
Pages (from-to)999-1006
Number of pages8
JournalMolecular Cell
Volume15
Issue number6
DOIs
StatePublished - Sep 24 2004

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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