1CA9

STRUCTURE OF TNF RECEPTOR ASSOCIATED FACTOR 2 IN COMPLEX WITH A PEPTIDE FROM TNF-R2

Summary for 1CA9

• Entry DOI: 10.2210/pdb1ca9/pdb
• Descriptor: PROTEIN (TNF RECEPTOR ASSOCIATED FACTOR 2), PROTEIN (TNF-R2) (3 entities in total)
• Functional Keywords: tnf signaling, traf, adapter protein, cell survival
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm : Q12933; Isoform 1: Cell membrane; Single-pass type I membrane protein. Isoform 2: Secreted. Tumor necrosis factor-binding protein 2: Secreted: P20333
• Total number of polymer chains: 8
• Total formula weight: 132490.37

Authors

Park, Y.C.,Burkitt, V.,Villa, A.R.,Tong, L.,Wu, H. (deposition date: 1999-02-25, release date: 1999-04-12, Last modification date: 2023-08-09)

Primary citation

Park, Y.C.,Burkitt, V.,Villa, A.R.,Tong, L.,Wu, H.
Structural basis for self-association and receptor recognition of human TRAF2.
Nature, 398:533-538, 1999

PubMed 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.

PubMed: 10206649
DOI: 10.1038/19110

Experimental method

X-RAY DIFFRACTION (2.3 Å)