The death domain superfamily in intracellular signaling of apoptosis and inflammation

Annu Rev Immunol. 2007;25:561-86. doi: 10.1146/annurev.immunol.25.022106.141656.


The death domain (DD) superfamily comprising the death domain (DD) subfamily, the death effector domain (DED) subfamily, the caspase recruitment domain (CARD) subfamily, and the pyrin domain (PYD) subfamily is one of the largest domain superfamilies. By mediating homotypic interactions within each domain subfamily, these proteins play important roles in the assembly and activation of apoptotic and inflammatory complexes. In this chapter, we review the molecular complexes assembled by these proteins, the structural and biochemical features of these domains, and the molecular interactions mediated by them. By analyzing the potential molecular basis for the function of these domains, we hope to provide a comprehensive understanding of the function, structure, interaction, and evolution of this important family of domains.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Apoptosis / immunology*
  • CARD Signaling Adaptor Proteins / genetics
  • CARD Signaling Adaptor Proteins / immunology*
  • Death Domain Receptor Signaling Adaptor Proteins / genetics
  • Death Domain Receptor Signaling Adaptor Proteins / immunology*
  • Evolution, Molecular*
  • Humans
  • Inflammation / genetics
  • Inflammation / immunology
  • Multiprotein Complexes / genetics
  • Multiprotein Complexes / immunology*
  • Protein Structure, Quaternary / genetics
  • Protein Structure, Tertiary / genetics
  • Signal Transduction / genetics
  • Signal Transduction / immunology*
  • Structure-Activity Relationship


  • CARD Signaling Adaptor Proteins
  • Death Domain Receptor Signaling Adaptor Proteins
  • Multiprotein Complexes