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PDBsum entry 1du3

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protein metals Protein-protein interface(s) links
Apoptosis PDB id
1du3
Jmol
Contents
Protein chains
90 a.a. *
110 a.a. *
(+ 0 more) 152 a.a. *
Metals
_ZN ×2
Waters ×162
* Residue conservation analysis
PDB id:
1du3
Name: Apoptosis
Title: Crystal structure of trail-sdr5
Structure: Death receptor 5. Chain: a, b, c, g, h, i. Fragment: extracellular domain. Engineered: yes. Tnf-related apoptosis inducing ligand. Chain: d, e, f, j, k, l. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Expressed in: bacteria. Expression_system_taxid: 2
Biol. unit: Hexamer (from PQS)
Resolution:
2.20Å     R-factor:   0.291     R-free:   0.291
Authors: S.-S.Cha,B.-J.Sung,B.-H.Oh
Key ref:
S.S.Cha et al. (2000). Crystal structure of TRAIL-DR5 complex identifies a critical role of the unique frame insertion in conferring recognition specificity. J Biol Chem, 275, 31171-31177. PubMed id: 10893238 DOI: 10.1074/jbc.M004414200
Date:
14-Jan-00     Release date:   27-Sep-00    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
O14763  (TR10B_HUMAN) -  Tumor necrosis factor receptor superfamily member 10B
Seq:
Struc:
440 a.a.
90 a.a.
Protein chains
Pfam   ArchSchema ?
O14763  (TR10B_HUMAN) -  Tumor necrosis factor receptor superfamily member 10B
Seq:
Struc:
440 a.a.
110 a.a.
Protein chains
Pfam   ArchSchema ?
P50591  (TNF10_HUMAN) -  Tumor necrosis factor ligand superfamily member 10
Seq:
Struc:
281 a.a.
152 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   1 term 
  Biological process     immune response   1 term 
  Biochemical function     TRAIL binding     2 terms  

 

 
DOI no: 10.1074/jbc.M004414200 J Biol Chem 275:31171-31177 (2000)
PubMed id: 10893238  
 
 
Crystal structure of TRAIL-DR5 complex identifies a critical role of the unique frame insertion in conferring recognition specificity.
S.S.Cha, B.J.Sung, Y.A.Kim, Y.L.Song, H.J.Kim, S.Kim, M.S.Lee, B.H.Oh.
 
  ABSTRACT  
 
TRAIL is a cytokine that induces apoptosis in a wide variety of tumor cells but rarely in normal cells. It contains an extraordinarily elongated loop because of an unique insertion of 12-16 amino acids compared with the other members of tumor necrosis factor family. Biological implication of the frame insertion has not been clarified. We have determined the crystal structure of TRAIL in a complex with the extracellular domain of death receptor DR5 at 2.2 A resolution. The structure reveals extensive contacts between the elongated loop and DR5 in an interaction mode that would not be allowed without the frame insertion. These interactions are missing in the structures of the complex determined by others recently. This observation, along with structure-inspired deletion analysis, identifies the critical role of the frame insertion as a molecular strategy conferring specificity upon the recognition of cognate receptors. The structure also suggests that a built-in flexibility of the tumor necrosis factor receptor family members is likely to play a general and important role in the binding and recognition of tumor necrosis factor family members.
 
  Selected figure(s)  
 
Figure 3.
Fig. 3. Superposition of the ligand-receptor complexes and that of sDR5 molecules. A, the TRAIL-sDR5 and TNF sTNFR55 complexes are superposed using only the structurally conserved C atoms on the -sheets of the ligand molecules. C atoms are shown with the omission of TNF . sDR5 and sTNFR55 are shown in green and violet, respectively. TRAIL is in light green. B, the six sDR5 molecules with the ordered B2 modules in three TRAIL-sDR5 complex structures are superposed, showing the variation in the relative position of the B2 module in CDR2.
Figure 4.
Fig. 4. The central contact region. A, surface representation of TRAIL-sDR5 exhibiting crevices at the binding interface that accommodate the penetration of the AA" loop. Positive, neutral, and negative electrostatic potentials are colored blue, white, and red, respectively. The molecular surfaces are drawn without residues 130-135, which is shown in sticks. Dots indicate a putative course of the disordered region starting from Leu-136 on the AA" loop. B, a simulated annealing 2F[o] F[c] omit map contoured at 1 . At a refinement stage with an R value of 25%, the structure was disturbed at 1000 K with the omission of residues 130-135 of the AA" loop and the residues within 3.5 Å from the segment, and then the map was calculated with the same omission. C, the interactions mediated by residues 131-135 of TRAIL. The intramolecular interaction of Arg-130 is not shown. The N1 module, CRD1, and CRD2 in sDR5 are represented by pink, yellow, and reddish brown, respectively. Residues 130-135 in TRAIL are in cyan. Oxygen and nitrogen atoms are in red and blue, respectively. White dotted lines indicate hydrogen bonds.
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2000, 275, 31171-31177) copyright 2000.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21300979 K.Hanada, Q.J.Wang, T.Inozume, and J.C.Yang (2011).
Molecular identification of an MHC-independent ligand recognized by a human {alpha}/{beta} T-cell receptor.
  Blood, 117, 4816-4825.  
21059944 H.M.Ta, G.T.Nguyen, H.M.Jin, J.Choi, H.Park, N.Kim, H.Y.Hwang, and K.K.Kim (2010).
Structure-based development of a receptor activator of nuclear factor-kappaB ligand (RANKL) inhibitor peptide and molecular basis for osteopetrosis.
  Proc Natl Acad Sci U S A, 107, 20281-20286.
PDB codes: 3nzy 3qbq
20156289 J.Vrielink, M.S.Heins, R.Setroikromo, E.Szegezdi, M.M.Mullally, A.Samali, and W.J.Quax (2010).
Synthetic constrained peptide selectively binds and antagonizes death receptor 5.
  FEBS J, 277, 1653-1665.  
19509255 D.V.Rozanov, A.Y.Savinov, V.S.Golubkov, O.L.Rozanova, T.I.Postnova, E.A.Sergienko, S.Vasile, A.E.Aleshin, M.F.Rega, M.Pellecchia, and A.Y.Strongin (2009).
Engineering a leucine zipper-TRAIL homotrimer with improved cytotoxicity in tumor cells.
  Mol Cancer Ther, 8, 1515-1525.  
18071905 M.Tarrus, A.M.van der Sloot, K.Temming, M.Lacombe, F.Opdam, W.J.Quax, G.Molema, K.Poelstra, and R.J.Kok (2008).
RGD-avidin-biotin pretargeting to alpha(v)beta (3) integrin enhances the proapoptotic activity of TNFalpha related apoptosis inducing ligand (TRAIL).
  Apoptosis, 13, 225-235.  
17671978 T.A.Wassenaar, W.J.Quax, and A.E.Mark (2008).
The conformation of the extracellular binding domain of Death Receptor 5 in the presence and absence of the activating ligand TRAIL: a molecular dynamics study.
  Proteins, 70, 333-343.  
17449269 F.K.Chan (2007).
Three is better than one: pre-ligand receptor assembly in the regulation of TNF receptor signaling.
  Cytokine, 37, 101-107.  
16731632 A.M.van der Sloot, V.Tur, E.Szegezdi, M.M.Mullally, R.H.Cool, A.Samali, L.Serrano, and W.J.Quax (2006).
Designed tumor necrosis factor-related apoptosis-inducing ligand variants initiating apoptosis exclusively via the DR5 receptor.
  Proc Natl Acad Sci U S A, 103, 8634-8639.  
16319225 L.Clancy, K.Mruk, K.Archer, M.Woelfel, J.Mongkolsapaya, G.Screaton, M.J.Lenardo, and F.K.Chan (2005).
Preligand assembly domain-mediated ligand-independent association between TRAIL receptor 4 (TR4) and TR2 regulates TRAIL-induced apoptosis.
  Proc Natl Acad Sci U S A, 102, 18099-18104.  
15711921 S.Bouralexis, D.M.Findlay, and A.Evdokiou (2005).
Death to the bad guys: targeting cancer via Apo2L/TRAIL.
  Apoptosis, 10, 35-51.  
16239906 S.W.Fesik (2005).
Promoting apoptosis as a strategy for cancer drug discovery.
  Nat Rev Cancer, 5, 876-885.  
15093829 G.Zhang (2004).
Tumor necrosis factor family ligand-receptor binding.
  Curr Opin Struct Biol, 14, 154-160.  
15562003 T.Mori, A.Oguro, T.Ohtsu, and Y.Nakamura (2004).
RNA aptamers selected against the receptor activator of NF-kappaB acquire general affinity to proteins of the tumor necrosis factor receptor family.
  Nucleic Acids Res, 32, 6120-6128.  
14656435 S.G.Hymowitz, D.M.Compaan, M.Yan, H.J.Wallweber, V.M.Dixit, M.A.Starovasnik, and A.M.de Vos (2003).
The crystal structures of EDA-A1 and EDA-A2: splice variants with distinct receptor specificity.
  Structure, 11, 1513-1520.
PDB codes: 1rj7 1rj8
11862220 D.A.Oren, Y.Li, Y.Volovik, T.S.Morris, C.Dharia, K.Das, O.Galperina, R.Gentz, and E.Arnold (2002).
Structural basis of BLyS receptor recognition.
  Nat Struct Biol, 9, 288-292.
PDB code: 1kxg
12392561 G.H.Nam, and K.Y.Choi (2002).
Association of human tumor necrosis factor-related apoptosis inducing ligand with membrane upon acidification.
  Eur J Biochem, 269, 5280-5287.  
11796220 J.L.Bodmer, P.Schneider, and J.Tschopp (2002).
The molecular architecture of the TNF superfamily.
  Trends Biochem Sci, 27, 19-26.  
  11581298 J.Lam, C.A.Nelson, F.P.Ross, S.L.Teitelbaum, and D.H.Fremont (2001).
Crystal structure of the TRANCE/RANKL cytokine reveals determinants of receptor-ligand specificity.
  J Clin Invest, 108, 971-979.
PDB code: 1jtz
11746948 R.L.Rich, and D.G.Myszka (2001).
Survey of the year 2000 commercial optical biosensor literature.
  J Mol Recognit, 14, 273-294.  
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.