PDBsum entry 2a9i

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protein metals links
Transferase PDB id
Protein chain
105 a.a. *
Waters ×145
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Molecular structure of the interleukin-1 receptor- associated kinase-4 death domain
Structure: Interleukin-1 receptor-associated kinase-4. Chain: a. Fragment: death domain. Synonym: irak-4. Engineered: yes
Source: Mus musculus. House mouse. Organism_taxid: 10090. Gene: irak4. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Biol. unit: Dimer (from PQS)
1.70Å     R-factor:   0.180     R-free:   0.223
Authors: M.V.Lasker,M.M.Gajjar,S.K.Nair
Key ref: M.V.Lasker et al. (2005). Cutting edge: molecular structure of the IL-1R-associated kinase-4 death domain and its implications for TLR signaling. J Immunol, 175, 4175-4179. PubMed id: 16177054
11-Jul-05     Release date:   11-Oct-05    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q8R4K2  (IRAK4_MOUSE) -  Interleukin-1 receptor-associated kinase 4
459 a.a.
105 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.  - Non-specific serine/threonine protein kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + a protein = ADP + a phosphoprotein
+ protein
+ phosphoprotein
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     signal transduction   1 term 


J Immunol 175:4175-4179 (2005)
PubMed id: 16177054  
Cutting edge: molecular structure of the IL-1R-associated kinase-4 death domain and its implications for TLR signaling.
M.V.Lasker, M.M.Gajjar, S.K.Nair.
IL-1R-associated kinase (IRAK) 4 is an essential component of innate immunity. IRAK-4 deficiency in mice and humans results in severe impairment of IL-1 and TLR signaling. We have solved the crystal structure for the death domain of Mus musculus IRAK-4 to 1.7 A resolution. This is the first glimpse of the structural details of a mammalian IRAK family member. The crystal structure reveals a six-helical bundle with a prominent loop, which among IRAKs and Pelle, a Drosophila homologue, is unique to IRAK-4. This highly structured loop contained between helices two and three, comprises an 11-aa stretch. Although innate immune domain recognition is thought to be very similar between Drosophila and mammals, this structural component points to a drastic difference. This structure can be used as a framework for future mutation and deletion studies and potential drug design.

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.  
20485341 S.C.Lin, Y.C.Lo, and H.Wu (2010).
Helical assembly in the MyD88-IRAK4-IRAK2 complex in TLR/IL-1R signalling.
  Nature, 465, 885-890.
PDB code: 3mop
19506249 H.Ohnishi, H.Tochio, Z.Kato, K.E.Orii, A.Li, T.Kimura, H.Hiroaki, N.Kondo, and M.Shirakawa (2009).
Structural basis for the multiple interactions of the MyD88 TIR domain in TLR4 signaling.
  Proc Natl Acad Sci U S A, 106, 10260-10265.
PDB code: 2z5v
  19498957 P.Towb, H.Sun, and S.A.Wasserman (2009).
Tube Is an IRAK-4 homolog in a Toll pathway adapted for development and immunity.
  J Innate Immun, 1, 309-321.  
19120483 T.P.Monie, M.C.Moncrieffe, and N.J.Gay (2009).
Structure and regulation of cytoplasmic adapter proteins involved in innate immune signaling.
  Immunol Rev, 227, 161-175.  
18794297 J.Fraczek, T.W.Kim, H.Xiao, J.Yao, Q.Wen, Y.Li, J.L.Casanova, J.Pryjma, and X.Li (2008).
The kinase activity of IL-1 receptor-associated kinase 4 is required for interleukin-1 receptor/toll-like receptor-induced TAK1-dependent NFkappaB activation.
  J Biol Chem, 283, 31697-31705.  
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.  
17362201 N.J.Gay, and M.Gangloff (2007).
Structure and function of Toll receptors and their ligands.
  Annu Rev Biochem, 76, 141-165.  
17943131 P.C.Sabeti, P.Varilly, B.Fry, J.Lohmueller, E.Hostetter, C.Cotsapas, X.Xie, E.H.Byrne, S.A.McCarroll, R.Gaudet, S.F.Schaffner, E.S.Lander, K.A.Frazer, D.G.Ballinger, D.R.Cox, D.A.Hinds, L.L.Stuve, R.A.Gibbs, J.W.Belmont, A.Boudreau, P.Hardenbol, S.M.Leal, S.Pasternak, D.A.Wheeler, T.D.Willis, F.Yu, H.Yang, C.Zeng, Y.Gao, H.Hu, W.Hu, C.Li, W.Lin, S.Liu, H.Pan, X.Tang, J.Wang, W.Wang, J.Yu, B.Zhang, Q.Zhang, H.Zhao, H.Zhao, J.Zhou, S.B.Gabriel, R.Barry, B.Blumenstiel, A.Camargo, M.Defelice, M.Faggart, M.Goyette, S.Gupta, J.Moore, H.Nguyen, R.C.Onofrio, M.Parkin, J.Roy, E.Stahl, E.Winchester, L.Ziaugra, D.Altshuler, Y.Shen, Z.Yao, W.Huang, X.Chu, Y.He, L.Jin, Y.Liu, Y.Shen, W.Sun, H.Wang, Y.Wang, Y.Wang, X.Xiong, L.Xu, M.M.Waye, S.K.Tsui, H.Xue, J.T.Wong, L.M.Galver, J.B.Fan, K.Gunderson, S.S.Murray, A.R.Oliphant, M.S.Chee, A.Montpetit, F.Chagnon, V.Ferretti, M.Leboeuf, J.F.Olivier, M.S.Phillips, S.Roumy, C.Sallée, A.Verner, T.J.Hudson, P.Y.Kwok, D.Cai, D.C.Koboldt, R.D.Miller, and L.Pawlikowska (2007).
Genome-wide detection and characterization of positive selection in human populations.
  Nature, 449, 913-918.  
17979850 S.Y.Zhang, E.Jouanguy, V.Sancho-Shimizu, H.von Bernuth, K.Yang, L.Abel, C.Picard, A.Puel, and J.L.Casanova (2007).
Human Toll-like receptor-dependent induction of interferons in protective immunity to viruses.
  Immunol Rev, 220, 225-236.  
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.  
  16741238 M.V.Lasker, S.M.Kuruvilla, M.M.Gajjar, A.Kapoor, and S.K.Nair (2006).
Metal ion-mediated reduction in surface entropy improves diffraction quality of crystals of the IRAK-4 death domain.
  J Biomol Tech, 17, 114-121.  
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
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.