2A5Y

Structure of a CED-4/CED-9 complex

Summary for 2A5Y

• Entry DOI: 10.2210/pdb2a5y/pdb
• Descriptor: Apoptosis regulator ced-9, ced-4, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: ced-4, ced-9, ced-3 activation, apoptosis
• Biological source: Caenorhabditis elegans; More
• Cellular location: Endomembrane system; Peripheral membrane protein: P41958; Mitochondrion : P30429
• Total number of polymer chains: 3
• Total formula weight: 150690.41

Authors

Yan, N.,Liu, Q.,Hao, Q.,Gu, L.,Shi, Y. (deposition date: 2005-07-01, release date: 2005-10-11, Last modification date: 2024-02-14)

Primary citation

Yan, N.,Chai, J.,Lee, E.S.,Gu, L.,Liu, Q.,He, J.,Wu, J.W.,Kokel, D.,Li, H.,Hao, Q.,Xue, D.,Shi, Y.
Structure of the CED-4-CED-9 complex provides insights into programmed cell death in Caenorhabditis elegans.
Nature, 437:831-837, 2005

PubMed 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 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.

PubMed: 16208361
DOI: 10.1038/nature04002

Experimental method

X-RAY DIFFRACTION (2.6 Å)