2:1 Stoichiometry of the Ced-4-ced-9 Complex and the Tetrameric Ced-4: Insights into the Regulation of Ced-3 Activation.
From: Department of Molecular Biology, Princeton University, Lewis Thomas Laboratory, Princeton, New Jersey 08544, USA.
Cell cycle (Georgetown, Tex.)
- Publish Date: Jan 2006
- ISSN: 1551-4005
- Volume: 5
- Issue: 1
- Pages: 31-4
- Medium: Internet
- Language: English
- Citation (JAMA): Yan Nieng, Xu Yanhui, Shi Yigong, et al. 2:1 Stoichiometry of the Ced-4-ced-9 Complex and the Tetrameric Ced-4: Insights into the Regulation of Ced-3 Activation.. Cell Cycle Jan 2006;5:31-4
Abstract
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.
Mesh Headings (Keywords): Animals, Apoptosis Regulatory Proteins, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Calcium-Binding Proteins, Caspases, Enzyme Activation, Multiprotein Complexes, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-bcl-2
Check for Full Text / PubMed Unique Identifier (PMID): 16294007
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