PDBsum entry 1fad

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Apoptosis PDB id
Protein chain
95 a.a. *
* Residue conservation analysis
PDB id:
Name: Apoptosis
Title: Death domain of fas-associated death domain protein, residues 89-183
Structure: Protein (fadd protein). Chain: a. Fragment: death domain (residues 89-183). Engineered: yes. Mutation: yes. Other_details: n-terminal extension of gly-ser-his-met from cloning artifact. Coordinates are not shown for artifact.
Source: Mus musculus. House mouse. Organism_taxid: 10090. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
NMR struc: 21 models
Authors: E.-J.Jeong,S.Bang,T.H.Lee,Y.-I.Park,W.-S.Sim,K.-S.Kim
Key ref:
E.J.Jeong et al. (1999). The solution structure of FADD death domain. Structural basis of death domain interactions of Fas and FADD. J Biol Chem, 274, 16337-16342. PubMed id: 10347191 DOI: 10.1074/jbc.274.23.16337
23-Mar-99     Release date:   06-Jul-99    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q61160  (FADD_MOUSE) -  FAS-associated death domain protein
205 a.a.
95 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     signal transduction   1 term 


DOI no: 10.1074/jbc.274.23.16337 J Biol Chem 274:16337-16342 (1999)
PubMed id: 10347191  
The solution structure of FADD death domain. Structural basis of death domain interactions of Fas and FADD.
E.J.Jeong, S.Bang, T.H.Lee, Y.I.Park, W.S.Sim, K.S.Kim.
A signal of Fas-mediated apoptosis is transferred through an adaptor protein Fas-associated death domain protein (FADD) by interactions between the death domains of Fas and FADD. To understand the signal transduction mechanism of Fas-mediated apoptosis, we solved the solution structure of a murine FADD death domain. It consists of six helices arranged in a similar fold to the other death domains. The interactions between the death domains of Fas and FADD analyzed by site-directed mutagenesis indicate that charged residues in helices alpha2 and alpha3 are involved in death domain interactions, and the interacting helices appear to interact in anti-parallel pattern, alpha2 of FADD with alpha3 of Fas and vice versa.
  Selected figure(s)  
Figure 3.
Fig. 3. Relative binding affinities of FADD-DD and its variants to Fas-DD. The binding affinity of each mutant is compared with wild type (WT) FADD-DD. Each mutant is constructed by replacing residues in helices 2 and 3 by either Ala or Asn. The binding affinities are shown in equilibrium association constants (K[a]) at pH 7.4. The mutations shown with no binding constants (R110A, K113A, R117A, E118A, V121N, and E123A) reduced binding affinity of FADD-DD by more than 10,000-folds, and affinity could not be estimated because of the weak binding. Self-association was estimated based on the binding between FADD and FADD-DD after 2 min of association in 10 m M HEPES buffer containing 150 mM NaCl, 3.4 mM EDTA, and 0.05% surfactant P20 at 25 °C. +, the self-association tendencies are indicated from the highest (++++) to the lowest (+).
Figure 4.
Fig. 4. The structure of proposed interaction sites of FADD-DD (left) and Fas-DD (19) (right). Positively charged residues are colored in blue, negatively charged residues are colored in red, and two hydrophobic residues (Leu^119, Val^121) are colored in sky blue. Only residues of FADD-DD studied by mutations are labeled. Residues with marginal effect on binding to Fas-DD are labeled in green. Val^121 is the corresponding residue at the position of lpr mutant in Fas. Helices 2 and 3 in FADD-DD and Fas-DD have the same charge distribution, suggesting that interaction between two death domains is in antiparallel pattern.
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (1999, 274, 16337-16342) copyright 1999.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21207148 H.H.Park (2011).
Structural analyses of death domains and their interactions.
  Apoptosis, 16, 209-220.  
20935634 L.Wang, J.K.Yang, V.Kabaleeswaran, A.J.Rice, A.C.Cruz, A.Y.Park, Q.Yin, E.Damko, S.B.Jang, S.Raunser, C.V.Robinson, R.M.Siegel, T.Walz, and H.Wu (2010).
The Fas-FADD death domain complex structure reveals the basis of DISC assembly and disease mutations.
  Nat Struct Mol Biol, 17, 1324-1329.
PDB code: 3oq9
20889682 M.Villa-Morales, E.González-Gugel, M.N.Shahbazi, J.Santos, and J.Fernández-Piqueras (2010).
Modulation of the Fas-apoptosis-signalling pathway by functional polymorphisms at Fas, FasL and Fadd and their implication in T-cell lymphoblastic lymphoma susceptibility.
  Carcinogenesis, 31, 2165-2171.  
19118384 F.L.Scott, B.Stec, C.Pop, M.K.Dobaczewska, J.J.Lee, E.Monosov, H.Robinson, G.S.Salvesen, R.Schwarzenbacher, and S.J.Riedl (2009).
The Fas-FADD death domain complex structure unravels signalling by receptor clustering.
  Nature, 457, 1019-1022.
PDB code: 3ezq
19203997 H.Z.Imtiyaz, X.Zhou, H.Zhang, D.Chen, T.Hu, and J.Zhang (2009).
The death domain of FADD is essential for embryogenesis, lymphocyte development, and proliferation.
  J Biol Chem, 284, 9917-9926.  
19679662 M.Loiarro, G.Gallo, N.Fantò, R.De Santis, P.Carminati, V.Ruggiero, and C.Sette (2009).
Identification of critical residues of the MyD88 death domain involved in the recruitment of downstream kinases.
  J Biol Chem, 284, 28093-28103.  
19582216 T.H.Jang, and H.H.Park (2009).
Purification, Crystallization and Preliminary X-ray Crystallographic Studies of RAIDD Death-Domain (DD).
  Int J Mol Sci, 10, 2501-2509.  
18931689 J.W.Yu, and Y.Shi (2008).
FLIP and the death effector domain family.
  Oncogene, 27, 6216-6227.  
17599096 B.J.Ferguson, D.Esposito, J.Jovanović, A.Sankar, P.C.Driscoll, and H.Mehmet (2007).
Biophysical and cell-based evidence for differential interactions between the death domains of CD95/Fas and FADD.
  Cell Death Differ, 14, 1717-1719.  
17201679 H.H.Park, Y.C.Lo, S.C.Lin, L.Wang, J.K.Yang, and H.Wu (2007).
The death domain superfamily in intracellular signaling of apoptosis and inflammation.
  Annu Rev Immunol, 25, 561-586.  
16977332 Q.Bao, and Y.Shi (2007).
Apoptosome: a platform for the activation of initiator caspases.
  Cell Death Differ, 14, 56-65.  
16710361 C.Sandu, G.Morisawa, I.Wegorzewska, T.Huang, A.F.Arechiga, J.M.Hill, T.Kim, C.M.Walsh, and M.H.Werner (2006).
FADD self-association is required for stable interaction with an activated death receptor.
  Cell Death Differ, 13, 2052-2061.  
16645484 E.López-Collazo, P.Fuentes-Prior, F.Arnalich, and C.del Fresno (2006).
Pathophysiology of interleukin-1 receptor-associated kinase-M: implications in refractory state.
  Curr Opin Infect Dis, 19, 237-244.  
16434054 H.H.Park, and H.Wu (2006).
Crystal structure of RAIDD death domain implicates potential mechanism of PIDDosome assembly.
  J Mol Biol, 357, 358-364.
PDB code: 2o71
16470584 J.Thakar, K.Schleinkofer, C.Borner, and T.Dandekar (2006).
RIP death domain structural interactions implicated in TNF-mediated proliferation and survival.
  Proteins, 63, 413-423.  
16003390 L.R.Thomas, L.M.Bender, M.J.Morgan, and A.Thorburn (2006).
Extensive regions of the FADD death domain are required for binding to the TRAIL receptor DR5.
  Cell Death Differ, 13, 160-162.  
17139086 N.Handa, M.Kukimoto-Niino, R.Akasaka, K.Murayama, T.Terada, M.Inoue, T.Yabuki, M.Aoki, E.Seki, T.Matsuda, E.Nunokawa, A.Tanaka, Y.Hayashizaki, T.Kigawa, M.Shirouzu, and S.Yokoyama (2006).
Structure of the UNC5H2 death domain.
  Acta Crystallogr D Biol Crystallogr, 62, 1502-1509.
PDB code: 1wmg
16762833 P.E.Carrington, C.Sandu, Y.Wei, J.M.Hill, G.Morisawa, T.Huang, E.Gavathiotis, Y.Wei, and M.H.Werner (2006).
The structure of FADD and its mode of interaction with procaspase-8.
  Mol Cell, 22, 599-610.
PDB code: 2gf5
17046227 Y.Shi (2006).
Mechanical aspects of apoptosome assembly.
  Curr Opin Cell Biol, 18, 677-684.  
15601308 Y.H.Soung, J.W.Lee, S.Y.Kim, S.W.Nam, W.S.Park, S.H.Kim, J.Y.Lee, N.J.Yoo, and S.H.Lee (2004).
Mutation of FADD gene is rare in human colon and stomach cancers.
  APMIS, 112, 595-597.  
15273313 Y.R.Chen, and A.C.Clark (2004).
Kinetic traps in the folding/unfolding of procaspase-1 CARD domain.
  Protein Sci, 13, 2196-2206.  
12576135 A.Clerk, S.M.Cole, T.E.Cullingford, J.G.Harrison, M.Jormakka, and D.M.Valks (2003).
Regulation of cardiac myocyte cell death.
  Pharmacol Ther, 97, 223-261.  
12456656 J.M.Hill, H.Vaidyanathan, J.W.Ramos, M.H.Ginsberg, and M.H.Werner (2002).
Recognition of ERK MAP kinase by PEA-15 reveals a common docking site within the death domain and death effector domain.
  EMBO J, 21, 6494-6504.
PDB code: 1n3k
11909948 K.Miki, and E.M.Eddy (2002).
Tumor necrosis factor receptor 1 is an ATPase regulated by silencer of death domain.
  Mol Cell Biol, 22, 2536-2543.  
11504623 C.H.Weber, and C.Vincenz (2001).
The death domain superfamily: a tale of two interfaces?
  Trends Biochem Sci, 26, 475-481.  
11231290 G.De Wilde, J.Murray-Rust, E.Boone, D.Olerenshaw, N.Q.McDonald, C.Ibanez, G.Haegeman, A.Wollmer, and M.Federwisch (2001).
Structure-activity relationship of the p55 TNF receptor death domain and its lymphoproliferation mutants.
  Eur J Biochem, 268, 1382-1391.  
11514682 W.J.Fairbrother, N.C.Gordon, E.W.Humke, K.M.O'Rourke, M.A.Starovasnik, J.P.Yin, and V.M.Dixit (2001).
The PYRIN domain: a member of the death domain-fold superfamily.
  Protein Sci, 10, 1911-1918.  
11051551 E.W.Humke, S.K.Shriver, M.A.Starovasnik, W.J.Fairbrother, and V.M.Dixit (2000).
ICEBERG: a novel inhibitor of interleukin-1beta generation.
  Cell, 103, 99.
PDB code: 1dgn
11114073 R.L.Rich, and D.G.Myszka (2000).
Skerra A, 2000. Engineered scaffolds for molecular recognition. Journal of Molecular Recognition13:167-187.
  J Mol Recognit, 13, 409-410.  
11057900 S.W.Fesik (2000).
Insights into programmed cell death through structural biology.
  Cell, 103, 273-282.  
10760153 S.W.Lee, Y.G.Ko, S.Bang, K.S.Kim, and S.Kim (2000).
Death effector domain of a mammalian apoptosis mediator, FADD, induces bacterial cell death.
  Mol Microbiol, 35, 1540-1549.  
10677501 T.Raveh, H.Berissi, M.Eisenstein, T.Spivak, and A.Kimchi (2000).
A functional genetic screen identifies regions at the C-terminal tail and death-domain of death-associated protein kinase that are critical for its proapoptotic activity.
  Proc Natl Acad Sci U S A, 97, 1572-1577.  
10589682 T.Xiao, P.Towb, S.A.Wasserman, and S.R.Sprang (1999).
Three-dimensional structure of a complex between the death domains of Pelle and Tube.
  Cell, 99, 545-555.
PDB code: 1d2z
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 code is shown on the right.