spacer
spacer
Go to PDB code: 
protein Protein-protein interface(s) links
Signaling protein PDB id
1kzz
Jmol
Contents
Protein chains
192 a.a. *
11 a.a. *
* Residue conservation analysis
PDB id:
1kzz
Name: Signaling protein
Title: Downstream regulator tank binds to the cd40 recognition site on traf3
Structure: Tnf receptor associated factor 3. Chain: a. Fragment: residues 377-568. Synonym: traf3, cd40 receptor associated factor 1, craf1, cd40 binding protein, cd40bp. Engineered: yes. Traf family member-associated nf-kappa-b activator. Chain: b.
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Expression_system_taxid: 562
Biol. unit: Tetramer (from PQS)
Resolution:
3.50Å     R-factor:   0.225     R-free:   0.307
Authors: C.Li,C.-Z.Ni,M.L.Havert,E.Cabezas,J.He,D.Kaiser,J.C.Reed, A.C.Satterthwait,G.Cheng,K.R.Ely
Key ref:
C.Li et al. (2002). Downstream regulator TANK binds to the CD40 recognition site on TRAF3. Structure, 10, 403-411. PubMed id: 12005438 DOI: 10.1016/S0969-2126(02)00733-5
Date:
08-Feb-02     Release date:   10-Apr-02    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q13114  (TRAF3_HUMAN) -  TNF receptor-associated factor 3
Seq:
Struc: 		 
Seq:
Struc: 		568 a.a.
192 a.a.
Protein chain
Pfam   ArchSchema ?
Q92844  (TANK_HUMAN) -  TRAF family member-associated NF-kappa-B activator
Seq:
Struc: 		425 a.a.
11 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 

 
DOI no: 10.1016/S0969-2126(02)00733-5 Structure 10:403-411 (2002)
PubMed id: 12005438  
 
 
Downstream regulator TANK binds to the CD40 recognition site on TRAF3.
C.Li, C.Z.Ni, M.L.Havert, E.Cabezas, J.He, D.Kaiser, J.C.Reed, A.C.Satterthwait, G.Cheng, K.R.Ely.
 
  ABSTRACT  
 
TRAFs (tumor necrosis factor receptor [TNFR]-associated factors) bind to the cytoplasmic portion of liganded TNFRs and stimulate activation of NF-kappaB or JNK pathways. A modulator of TRAF signaling, TANK, serves as either an enhancer or an inhibitor of TRAF-mediated signaling pathways. The crystal structure of a region of TANK bound to TRAF3 has been determined and compared to a similar CD40/TRAF3 complex. TANK and CD40 bind to the same crevice on TRAF3. The recognition motif PxQxT is presented in a boomerang-like structure in TANK that is markedly different from the hairpin loop that forms in CD40 upon binding to TRAF3. Critical TANK contact residues were confirmed by mutagenesis to be required for binding to TRAF3 or TRAF2. Binding affinity, measured by isothermal titration calorimetry and competition assays, demonstrated that TANK competes with CD40 for the TRAF binding site.
 
  Selected figure(s)  
 
Figure 7.
Figure 7. Ball-and-Stick Model of TIM2 Fitted to Electron Density from Cosoaking Experiment with CD40 PeptideThe density clearly revealed the "boomerang" configuration of TIM2 rather than the "hairpin" shape characteristic of CD40 when bound to TRAF3 [26]. A stereo view of the 3.0 Å 2F[o] -F[c] difference map is shown with the TRAF3 model as a wire model.
 
  The above figure is reprinted by permission from Cell Press: Structure (2002, 10, 403-411) copyright 2002.  
  Figure was selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19893624 P.Nakhaei, T.Mesplede, M.Solis, Q.Sun, T.Zhao, L.Yang, T.H.Chuang, C.F.Ware, R.Lin, and J.Hiscott (2009).
The E3 ubiquitin ligase Triad3A negatively regulates the RIG-I/MAVS signaling pathway by targeting TRAF3 for degradation.
  PLoS Pathog, 5, e1000650.  
19668221 T.Kawagoe, O.Takeuchi, Y.Takabatake, H.Kato, Y.Isaka, T.Tsujimura, and S.Akira (2009).
TANK is a negative regulator of Toll-like receptor signaling and is critical for the prevention of autoimmune nephritis.
  Nat Immunol, 10, 965-972.  
18439848 M.C.Michallet, E.Meylan, M.A.Ermolaeva, J.Vazquez, M.Rebsamen, J.Curran, H.Poeck, M.Bscheider, G.Hartmann, M.König, U.Kalinke, M.Pasparakis, and J.Tschopp (2008).
TRADD protein is an essential component of the RIG-like helicase antiviral pathway.
  Immunity, 28, 651-661.  
16825662 J.H.Thomas (2006).
Adaptive evolution in two large families of ubiquitin-ligase adapters in nematodes and plants.
  Genome Res, 16, 1017-1030.  
16858409 S.K.Saha, E.M.Pietras, J.Q.He, J.R.Kang, S.Y.Liu, G.Oganesyan, A.Shahangian, B.Zarnegar, T.L.Shiba, Y.Wang, and G.Cheng (2006).
Regulation of antiviral responses by a direct and specific interaction between TRAF3 and Cardif.
  EMBO J, 25, 3257-3263.  
16085652 E.Santelli, M.Leone, C.Li, T.Fukushima, N.E.Preece, A.J.Olson, K.R.Ely, J.C.Reed, M.Pellecchia, R.C.Liddington, and S.Matsuzawa (2005).
Structural analysis of Siah1-Siah-interacting protein interactions and insights into the assembly of an E3 ligase multiprotein complex.
  J Biol Chem, 280, 34278-34287.
PDB codes: 2a25 2a26
16009714 S.Wu, P.Xie, K.Welsh, C.Li, C.Z.Ni, X.Zhu, J.C.Reed, A.C.Satterthwait, G.A.Bishop, and K.R.Ely (2005).
LMP1 protein from the Epstein-Barr virus is a structural CD40 decoy in B lymphocytes for binding to TRAF3.
  J Biol Chem, 280, 33620-33626.
PDB code: 1zms
15808506 V.Saridakis, Y.Sheng, F.Sarkari, M.N.Holowaty, K.Shire, T.Nguyen, R.G.Zhang, J.Liao, W.Lee, A.M.Edwards, C.H.Arrowsmith, and L.Frappier (2005).
Structure of the p53 binding domain of HAUSP/USP7 bound to Epstein-Barr nuclear antigen 1 implications for EBV-mediated immortalization.
  Mol Cell, 18, 25-36.
PDB codes: 1yy6 1yze
14517219 C.Li, P.S.Norris, C.Z.Ni, M.L.Havert, E.M.Chiong, B.R.Tran, E.Cabezas, J.C.Reed, A.C.Satterthwait, C.F.Ware, and K.R.Ely (2003).
Structurally distinct recognition motifs in lymphotoxin-beta receptor and CD40 for tumor necrosis factor receptor-associated factor (TRAF)-mediated signaling.
  J Biol Chem, 278, 50523-50529.
PDB code: 1rf3
12783577 J.M.Zapata (2003).
TNF-receptor-associated factors as targets for drug development.
  Expert Opin Ther Targets, 7, 411-425.  
14732929 M.J.Cliff, and J.E.Ladbury (2003).
A survey of the year 2002 literature on applications of isothermal titration calorimetry.
  J Mol Recognit, 16, 383-391.  
  12787559 P.W.Dempsey, S.E.Doyle, J.Q.He, and G.Cheng (2003).
The signaling adaptors and pathways activated by TNF superfamily.
  Cytokine Growth Factor Rev, 14, 193-209.  
12351847 H.Ye, M.Cirilli, and H.Wu (2002).
The use of construct variation and diffraction data analysis in the crystallization of the TRAF domain of human tumor necrosis factor receptor associated factor 6.
  Acta Crystallogr D Biol Crystallogr, 58, 1886-1888.  
12447905 K.R.Ely, and C.Li (2002).
Structurally adaptive hot spots at a protein interaction interface on TRAF3.
  J Mol Recognit, 15, 286-290.  
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. Where a reference describes a PDB structure, the PDB codes are shown on the right.