PDBsum entry 3knv

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protein metals links
Signaling protein PDB id
Protein chain
123 a.a. *
_ZN ×3
Waters ×92
* Residue conservation analysis
PDB id:
Name: Signaling protein
Title: Crystal structure of the ring and first zinc finger domains of traf2
Structure: Tnf receptor-associated factor 2. Chain: a. Fragment: ring and the first zinc finger domains: unp residues 1-133. Synonym: tumor necrosis factor type 2 receptor-associated protein 3. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: traf2, trap3. Expressed in: escherichia coli. Expression_system_taxid: 562.
1.90Å     R-factor:   0.216     R-free:   0.239
Authors: Q.Yin,H.Wu
Key ref: Q.Yin et al. (2009). Structural basis for the lack of E2 interaction in the RING domain of TRAF2. Biochemistry, 48, 10558-10567. PubMed id: 19810754
12-Nov-09     Release date:   24-Nov-09    
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Protein chain
Pfam   ArchSchema ?
Q12933  (TRAF2_HUMAN) -  TNF receptor-associated factor 2
501 a.a.
123 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 3 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     regulation of apoptotic process   5 terms 
  Biochemical function     metal ion binding     3 terms  


Biochemistry 48:10558-10567 (2009)
PubMed id: 19810754  
Structural basis for the lack of E2 interaction in the RING domain of TRAF2.
Q.Yin, B.Lamothe, B.G.Darnay, H.Wu.
TRAF proteins are intracellular signal transducers for a number of immune receptor superfamilies. Specifically, TRAF2 interacts with members of the TNF receptor superfamily and connects the receptors to downstream signaling proteins. It has been assumed that TRAF2 is a ubiquitin ligase like TRAF6 and mediates K63-linked polyubiquitination of RIP1, a kinase pivotal in TNFalpha-induced NF-kappaB activation. Here we report the crystal structure of the RING and the first zinc finger domains of TRAF2. We show that the TRAF2 RING structure is very different from the known TRAF6 RING structure. The differences are multifaceted, including amino acid differences at the critical Ubc13-interacting site, local conformational differences, and a unique nine-residue insertion between the RING domain and the first zinc finger in TRAF2. These structural differences prevent TRAF2 from interacting with Ubc13 and other related E2s via steric clash and unfavorable interfaces. Our structural observation should prompt a re-evaluation of the role of TRAF2 in TNFalpha signaling and may indicate that TRAF2-associated proteins such as cIAPs may be the ubiquitin ligases for NF-kappaB signaling.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21660053 H.Häcker, P.H.Tseng, and M.Karin (2011).
Expanding TRAF function: TRAF3 as a tri-faced immune regulator.
  Nat Rev Immunol, 11, 457-468.  
21232017 H.Wajant, and P.Scheurich (2011).
TNFR1-induced activation of the classical NF-κB pathway.
  FEBS J, 278, 862-876.  
21512573 T.Pertel, S.Hausmann, D.Morger, S.Züger, J.Guerra, J.Lascano, C.Reinhard, F.A.Santoni, P.D.Uchil, L.Chatel, A.Bisiaux, M.L.Albert, C.Strambio-De-Castillia, W.Mothes, M.Pizzato, M.G.Grütter, and J.Luban (2011).
TRIM5 is an innate immune sensor for the retrovirus capsid lattice.
  Nature, 472, 361-365.  
21113135 J.N.Dynek, T.Goncharov, E.C.Dueber, A.V.Fedorova, A.Izrael-Tomasevic, L.Phu, E.Helgason, W.J.Fairbrother, K.Deshayes, D.S.Kirkpatrick, and D.Vucic (2010).
c-IAP1 and UbcH5 promote K11-linked polyubiquitination of RIP1 in TNF signalling.
  EMBO J, 29, 4198-4209.  
20817427 P.D.Mace, and S.J.Riedl (2010).
Molecular cell death platforms and assemblies.
  Curr Opin Cell Biol, 22, 828-836.  
20577214 S.E.Alvarez, K.B.Harikumar, N.C.Hait, J.Allegood, G.M.Strub, E.Y.Kim, M.Maceyka, H.Jiang, C.Luo, T.Kordula, S.Milstien, and S.Spiegel (2010).
Sphingosine-1-phosphate is a missing cofactor for the E3 ubiquitin ligase TRAF2.
  Nature, 465, 1084-1088.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time.