J Biol Chem. 2005 Sep 9;280(36):31974-80. Epub 2005 Jul 8.

A mechanism for death receptor discrimination by death adaptors.External

Sandu, C., Gavathiotis, E., Huang, T., Wegorzewska, I., Werner, M. H.,
--- - Laboratory of Molecular Biophysics, The Rockefeller University, New York, New York 10021, USA.
The death domain and death effector domain are two common motifs that mediate protein-protein interactions between components of cell death signaling complexes. The mechanism by which these domains engage their binding partners has been explored by extensive mutagenesis of two death adaptors, FADD and TRADD, suggesting that a death adaptor can discriminate its intended binding partners from other proteins harboring similar motifs. Death adaptors are found to utilize one of two topologically conserved surfaces for protein-protein interaction, whether that partner is another adaptor or its cognate receptor. These surfaces are topologically related to the interaction between death domains observed in the x-ray crystal structure of the Drosophila adaptor Tube bound to Pelle kinase. Comparing the topology of protein-protein interactions for FADD complexes to TRADD complexes reveals that FADD uses a Tube-like surface in each of its death motifs to engage either CD95 or TRADD. TRADD reverses these roles, employing a Pelle-like surface to interact with either receptor TNFR1 or adaptor FADD. Since death adaptors display a Tube-like or Pelle-like preference for engaging their binding partners, Tube/Pelle-like pairing provides a mechanism for death adaptor discrimination of death receptors.
PMID: 16006552External
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
In vitro interaction
  DD1 DD2 Reference
Family DD1 DD2 Method Species Region Expression Species Region Expression
DD FADD Link TRADD GST fusion protein pull-down Not specified Full length E.coli Not specified 243-455 In vitro translation 16006552
DD TNFR1 Link TRADD GST fusion protein pull-down Not specified 195-312 E.coli Not specified 243-455 In vitro translation 16006552
(Link: click this icon to show interactions only between the two corresponding DDs)
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
Characterization
  Stoichiometry Affinity Protein-Protein interface Reference
Family DD1 DD2 Method Mutation Complex structure
DD FADD Link TRADD GST fusion protein pull-down D246R, E255R, Q267A, R278A (TRADD) R113E, R117E, D123R, D175R (FADD) 16006552
DD TNFR1 Link TRADD GST fusion protein pull-down Q220E, R224E, D246R, F266E, Q267A, A275D (TRADD) R341E, R437A, G403E, E406R (TNFR1) 16006552
(Link: click this icon to show interactions only between the two corresponding DDs)