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- Title
Structure of the CED-4–CED-9 complex provides insights into programmed cell death in Caenorhabditis elegans.
- Authors
Nieng Yan; Chai, Jijie; Eui Seung Lee; Lichuan Gu; Qun Liu; Jiaqing He; Jia-Wei Wu; Kokel, David; Huilin Li; Quan Hao; Ding Xue; Yigong Shi
- Abstract
Interplay among four genes—egl-1, ced-9, ced-4 and ced-3—controls the onset of programmed cell death in the nematode Caenorhabditis elegans. Activation of the cell-killing protease CED-3 requires CED-4. However, CED-4 is constitutively inhibited by CED-9 until its release by EGL-1. Here we report the crystal structure of the CED-4–CED-9 complex at 2.6 Å resolution, and a complete reconstitution of the CED-3 activation pathway using homogeneous proteins of CED-4, CED-9 and EGL-1. One molecule of CED-9 binds to an asymmetric dimer of CED-4, but specifically recognizes only one of the two CED-4 molecules. This specific interaction prevents CED-4 from activating CED-3. EGL-1 binding induces pronounced conformational changes in CED-9 that result in the dissociation of the CED-4 dimer from CED-9. The released CED-4 dimer further dimerizes to form a tetramer, which facilitates the autoactivation of CED-3. Together, our studies provide important insights into the regulation of cell death activation in C. elegans.
- Subjects
GENES; CELL death; CELLS; CAENORHABDITIS elegans; CAENORHABDITIS; PROTEINS; MOLECULES
- Publication
Nature, 2005, Vol 437, Issue 7060, p831
- ISSN
0028-0836
- Publication type
Article
- DOI
10.1038/nature04002