Tumour @entity39 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 @entity1473 -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 @entity1 @entity9134 , both alone and in complex with a peptide from @entity10733 ( @entity10733 ). 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 @entity10733 peptide binds to a conserved shallow surface @entity308 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 @entity9134 -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.

Structural basis for self-association and receptor recognition of @entity1 XXXX .

@entity1 :: ('9606', 'Species') :: ['human'] @entity308 :: ('MESH:D003866', 'Disease') :: ['depression'] @entity39 :: ('MESH:D009336', 'Disease') :: ['necrosis'] @entity10733 :: ('7133', 'Gene') :: ['TNF receptor-2', 'TNF-R2'] @entity9134 :: ('7186', 'Gene') :: ['TRAF2'] @entity1473 :: ('CHEBI:46883', 'Chemical') :: ['carboxy']
@entity9134 :: (7186,Gene) :: ['TRAF2']
