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

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

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

Nature. 1999 Apr 8;398(6727):533-8.

PubMed ID

10206649 [ View in PubMed

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Abstract

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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Etanercept	Tumor necrosis factor	Protein	Humans	Yes	Inhibitor Antibody	Details

Polypeptides

Name	UniProt ID
Tumor necrosis factor receptor superfamily member 1B	P20333	Details