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Structural basis for self-association and receptor recognition of human TRAF2.

Tumour necrosis factor (TNF)-receptor-associated factors (TRAFs) form a family of cytoplasmic adapter proteins that mediate signal transduction from many members of the TNF-receptor superfamily and the interleukin-1 receptor. They are important in the regulation of cell survival and cell death. The carboxy-terminal region of TRAFs (the TRAF domain) is required for self-association and interaction with receptors. The domain contains a predicted coiled-coil region that is followed by a highly conserved TRAF-C domain. Here we report the crystal structure of the TRAF domain of human TRAF2, both alone and in complex with a peptide from TNF receptor-2 (TNF-R2). The structures reveal a trimeric self-association of the TRAF domain, which we confirm by studies in solution. The TRAF-C domain forms a new, eight-stranded antiparallel beta-sandwich structure. The TNF-R2 peptide binds to a conserved shallow surface depression on one TRAF-C domain and does not contact the other protomers of the trimer. The nature of the interaction indicates that an SXXE motif may be a TRAF2-binding consensus sequence. The trimeric structure of the TRAF domain provides an avidity-based explanation for the dependence of TRAF recruitment on the oligomerization of the receptors by their trimeric extracellular ligands.

Pubmed ID: 10206649


  • Park YC
  • Burkitt V
  • Villa AR
  • Tong L
  • Wu H



Publication Data

April 8, 1999

Associated Grants


Mesh Terms

  • Amino Acid Sequence
  • Cloning, Molecular
  • Crystallography, X-Ray
  • Escherichia coli
  • Humans
  • Macromolecular Substances
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Binding
  • Protein Conformation
  • Proteins
  • Receptors, Tumor Necrosis Factor
  • Recombinant Proteins
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • Structure-Activity Relationship
  • TNF Receptor-Associated Factor 2