1E41

Death domain from human FADD/MORT1

Summary for 1E41

• Entry DOI: 10.2210/pdb1e41/pdb
• Related: 1A1W 1A1Z 1E3Y
• Descriptor: FADD PROTEIN (1 entity in total)
• Functional Keywords: apoptosis, death domain, adapter molecule, fas receptor death inducing signalling complex
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 1
• Total formula weight: 11870.37

Authors

Driscoll, P.C.,Berglund, H.,Olerenshaw, D.,McDonald, N.Q. (deposition date: 2000-06-27, release date: 2000-11-06, Last modification date: 2024-05-15)

Primary citation

Berglund, H.,Olerenshaw, D.,Sankar, A.,Federwisch, M.,Mcdonald, N.Q.,Driscoll, P.C.
The Three-Dimensional Solution Structure and Dynamic Properties of the Human Fadd Death Domain
J.Mol.Biol., 302:171-, 2000

PubMed Abstract: FADD (also known as MORT-1) is an essential adapter protein that couples the transmembrane receptors Fas (CD95) and tumor necrosis factor receptor-1 (TNF-R1) to intracellular cysteine proteases known as caspases, which propagate and execute the programmed cell death-inducing signal triggered by Fas ligand (FasL, CD95L) and TNF. FADD contains 208 amino acid residues, and comprises two functionally and structurally distinct domains: an N-terminal death effector domain (DED) that promotes activation of the downstream proteolytic cascade through binding of the DED domains of procaspase-8; and a C-terminal death domain (DD). FADD-DD provides the site of FADD recruitment to death receptor complexes at the plasma membrane by, for example, interaction with the Fas receptor cytoplasmic death domain (Fas-DD), or binding of the TNF-R1 adapter molecule TRADD. We have determined the three-dimensional solution structure and characterised the internal polypeptide dynamics of human FADD-DD using heteronuclear NMR spectroscopy of (15)N and (13)C,(15)N-labelled samples. The structure comprises six alpha-helices joined by short loops and displays overall similarity to the death domain of the Fas receptor. The analysis of the dynamic properties reveals no evidence of contiguous stretches of polypeptide chain with increased internal motion, except at the extreme chain termini. A pattern of increased rates of amide proton solvent exchange in the alpha3 helix correlates with a higher degree of solvent exposure for this secondary structure element. The properties of the FADD-DD structure are discussed with respect to previously reported mutagenesis data and emerging models for FasL-induced FADD recruitment to Fas and caspase-8 activation.

PubMed: 10964568
DOI: 10.1006/JMBI.2000.4011

Experimental method

SOLUTION NMR