@article{168321,
  keywords = {Animals, Caenorhabditis elegans, Enzyme Activation, Multiprotein Complexes, Caenorhabditis elegans Proteins, Calcium-Binding Proteins, Proto-Oncogene Proteins, Apoptosis Regulatory Proteins, Proto-Oncogene Proteins c-bcl-2, Caspases},
  author = {Nieng Yan and Yanhui Xu and Yigong Shi},
  title = {2:1 Stoichiometry of the CED-4-CED-9 complex and the tetrameric CED-4: insights into the regulation of CED-3 activation},
  abstract = {<p>Four evolutionally conserved proteins -EGL-1, CED-9, CED-4 and CED-3- collectively control the initiation of programmed cell death (PCD) in Caenorhabditis elegans. Activation of CED-3, the cell killing caspase, requires CED-4. The pro-death function of CED-4 is inhibited by the mitochondria-bound CED-9. Crystal structure of the 150-kDa CED-4-CED-9 complex at 2.6 A resolution reveals a 2:1 stoichiometry between CED-4 and CED-9. EGL-1 binding to CED-9 results in the dissociation of CED-4 from the CED-4-CED-9 complex. The freed CED-4 dimer further dimerizes to form a tetramer. Only the CED-4 tetramer, but not dimer or monomer, is capable of activating CED-3. Thus, CED-9 inhibits CED-4-mediated activation of CED-3 by sequestering CED-4 dimer from further dimerization. On the basis of structural and biochemical analyses, working models are proposed to explain the mechanism by which CED-4 facilitates CED-3 activation.</p>
},
  year = {2006},
  journal = {Cell Cycle},
  volume = {5},
  pages = {31-4},
  month = {01/2006},
  issn = {1551-4005},
  doi = {10.4161/cc.5.1.2263},
  language = {eng},
}