@article{168476,
  keywords = {Animals, Models, Molecular, Adenosine Triphosphate, Binding Sites, Substrate Specificity, Repressor Proteins, Caenorhabditis elegans, Protein Binding, Enzyme Activation, Multiprotein Complexes, Caenorhabditis elegans Proteins, Calcium-Binding Proteins, Apoptosis, Proto-Oncogene Proteins, Protein Structure, Quaternary, Apoptosis Regulatory Proteins, Proto-Oncogene Proteins c-bcl-2, Caspases},
  author = {Nieng Yan and Jijie Chai and Eui Seung Lee and Lichuan Gu and Qun Liu and Jiaqing He and Jia-Wei Wu and David Kokel and Huilin Li and Quan Hao and Ding Xue and Yigong Shi},
  title = {Structure of the CED-4-CED-9 complex provides insights into programmed cell death in Caenorhabditis elegans},
  abstract = {<p>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 A 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.</p>
},
  year = {2005},
  journal = {Nature},
  volume = {437},
  pages = {831-7},
  month = {10/2005},
  issn = {1476-4687},
  doi = {10.1038/nature04002},
  language = {eng},
}