A mechanism for death receptor discrimination by death adaptors

Cristinel Sandu, Evripidis Gavathiotis, Ted Huang, Iga Wegorzewska, Milton H. Werner

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)31974-31980
Number of pages7
JournalJournal of Biological Chemistry
Volume280
Issue number36
DOIs
StatePublished - Sep 9 2005
Externally publishedYes

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Death Domain Receptors
Proteins
Receptors, Tumor Necrosis Factor, Type I
Mutagenesis
Amino Acid Motifs
Cell death
Drosophila
Membrane Proteins
Cell Death
Phosphotransferases
Crystal structure
Topology
X-Rays
X rays

ASJC Scopus subject areas

  • Biochemistry

Cite this

A mechanism for death receptor discrimination by death adaptors. / Sandu, Cristinel; Gavathiotis, Evripidis; Huang, Ted; Wegorzewska, Iga; Werner, Milton H.

In: Journal of Biological Chemistry, Vol. 280, No. 36, 09.09.2005, p. 31974-31980.

Research output: Contribution to journalArticle

Sandu, Cristinel ; Gavathiotis, Evripidis ; Huang, Ted ; Wegorzewska, Iga ; Werner, Milton H. / A mechanism for death receptor discrimination by death adaptors. In: Journal of Biological Chemistry. 2005 ; Vol. 280, No. 36. pp. 31974-31980.
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