 The Death Domain | |
|
| Class:Apoptosis | |
|
Structure:
 Death domains are the founding members of the death-fold superfamily comprising DD, DED and CARD modules. The death fold consists of a six helical bundle with three stacked pairs of helices packed in an antiparallel manner. The helices enclose a tightly packed hydrophobic core. Charges are polarized with three helices (1,4,3) forming one side of the bundle with primarily basic residues and (2,5,6) forming the primarily acidic opposite side. In true modular fashion, N and C termini are in close proximity. The structure of the death domain of FADD is shown.
Structure Reference:
Jeong, EJ. et al. (1999) J. Biol. Chem. 274 (23): 16337-42. PDB: 1FAD.
| |
|
Domain binding and function:
Death domains (DD) are 80-100 residue long motifs involved in apoptotic signal transduction. They are found both in cytoplasmic proteins and in transmembrane proteins of the tumor necrosis factor receptor superfamily. Death domains serve as recruiting modules through their ability to heterodimerize with the Death domains of distinct proteins, including adaptor proteins such as FADD, bringing various components into a larger signaling complex.
Due to the significant polarization of charged residues on the surface of the death domain, dimerization is believed to arise primarily through electrostatic interactions. Dimerization has been shown to be specific and is thought to arise through specific complementary charge patterns on dimerization partners.
| |
|
Examples of Proteins:
| TNF Receptors |
|
Adaptors |
| Fas, TRAIL R1 |  |
FADD |
| Fas | |
RIP |
| TNF-R55 | |
TRADD |
|
|
|
| |
|
Referenced in part on Cell Signaling Technology Website, Reference Section on Protein Domains. We gratefully acknowledge the following contributors:
Piers Nash1, Dan Lin3, Kathleen Binns2, Clark Wells2, Rob Ingham2, Terry Kubiseski2, Bernard Liu1, Matt Smith2,3, Ivan Blasutig2,3, Maria Sierra1, Caesar Lim2,3, Michael Arc1, Jim Fawcett2 and Tony Pawson2,3.
1. Ben May Institute for Cancer Research, The University of Chicago, Chicago, Illinois, 60637, USA
2. Program in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, M5G 1X5, Canada
3. Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario, M5S 1A8, Canada
| |
|
