PDBsum entry 1o77

Go to PDB code: 
protein Protein-protein interface(s) links
Immune system/membrane protein PDB id
Protein chain
141 a.a. *
* Residue conservation analysis
PDB id:
Name: Immune system/membrane protein
Title: Crystal structure of the c713s mutant of the tir domain of human tlr2
Structure: Toll-like receptor 2. Chain: a, b, c, d, e. Fragment: tir domain, residues 639-784. Synonym: toll/interleukin 1 receptor-like protein 4, tlr2, til4. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 469008.
3.20Å     R-factor:   0.249     R-free:   0.315
Authors: X.Tao,Y.Xu,Z.Ye,A.A.Beg,L.Tong
Key ref: X.Tao et al. (2002). An extensively associated dimer in the structure of the C713S mutant of the TIR domain of human TLR2. Biochem Biophys Res Commun, 299, 216-221. PubMed id: 12437972 DOI: 10.1016/S0006-291X(02)02581-0
24-Oct-02     Release date:   21-Nov-02    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
O60603  (TLR2_HUMAN) -  Toll-like receptor 2
784 a.a.
141 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!
  Cellular component     integral to membrane   1 term 
  Biological process     signal transduction   8 terms 


DOI no: 10.1016/S0006-291X(02)02581-0 Biochem Biophys Res Commun 299:216-221 (2002)
PubMed id: 12437972  
An extensively associated dimer in the structure of the C713S mutant of the TIR domain of human TLR2.
X.Tao, Y.Xu, Y.Zheng, A.A.Beg, L.Tong.
The Toll/interleukin-1 receptor (TIR) domains are conserved modules in the intracellular regions of the Toll-like receptors (TLRs) and interleukin-1 receptors (IL-1Rs). The domains are crucial for the signal transduction by these receptors, through homotypic interactions among the receptor and the downstream adapter TIR domains. Previous studies showed that the BB loop in the structure of the TIR domain forms a prominent conserved feature on the surface and is important for receptor signaling. Here we report the crystal structure of the C713S mutant of the TIR domain of human TLR2. An extensively associated dimer is observed in the crystal structure and mutations of several residues in this dimer interface abolished the function of the receptor. Moreover, the structure shows that the BB loop can adopt different conformations, which are required for the formation of this dimer. This asymmetric dimer might represent the TLR2:TLRx heterodimer in the function of this receptor.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21280117 E.S.Henriques, R.M.Brito, H.Soares, S.Ventura, Oliveira, and R.M.Parkhouse (2011).
Modeling of the Toll-like receptor 3 and a putative Toll-like receptor 3 antagonist encoded by the African swine fever virus.
  Protein Sci, 20, 247-255.  
21481769 I.Botos, D.M.Segal, and D.R.Davies (2011).
The Structural Biology of Toll-like Receptors.
  Structure, 19, 447-459.  
20354830 H.Ohnishi, H.Tochio, Z.Kato, T.Kimura, H.Hiroaki, N.Kondo, and M.Shirakawa (2010).
1H, 13C, and 15N resonance assignment of the TIR domain of human MyD88.
  Biomol NMR Assign, 4, 123-125.  
19470169 M.R.Bhide, R.Mucha, I.Mikula, L.Kisova, R.Skrabana, M.Novak, and I.Mikula (2009).
Novel mutations in TLR genes cause hyporesponsiveness to Mycobacterium avium subsp. paratuberculosis infection.
  BMC Genet, 10, 21.  
19277504 S.I.Ahn, J.K.Lee, and H.S.Youn (2009).
Inhibition of homodimerization of toll-like receptor 4 by 6-shogaol.
  Mol Cells, 27, 211-215.  
19535337 S.L.Chan, L.Y.Low, S.Hsu, S.Li, T.Liu, E.Santelli, G.Le Negrate, J.C.Reed, V.L.Woods, and J.Pascual (2009).
Molecular Mimicry in Innate Immunity: CRYSTAL STRUCTURE OF A BACTERIAL TIR DOMAIN.
  J Biol Chem, 284, 21386-21392.
PDB code: 3h16
19648648 S.W.Wong, M.J.Kwon, A.M.Choi, H.P.Kim, K.Nakahira, and D.H.Hwang (2009).
Fatty acids modulate Toll-like receptor 4 activation through regulation of receptor dimerization and recruitment into lipid rafts in a reactive oxygen species-dependent manner.
  J Biol Chem, 284, 27384-27392.  
18810334 T.Xiao (2009).
Innate immune recognition of nucleic acids.
  Immunol Res, 43, 98.  
18256479 H.S.Youn, H.J.Lim, H.J.Lee, D.Hwang, M.Yang, R.Jeon, and J.H.Ryu (2008).
Garlic (Allium sativum) extract inhibits lipopolysaccharide-induced Toll-like receptor 4 dimerization.
  Biosci Biotechnol Biochem, 72, 368-375.  
18332149 T.Nyman, P.Stenmark, S.Flodin, I.Johansson, M.Hammarström, and P.Nordlund (2008).
The crystal structure of the human toll-like receptor 10 cytoplasmic domain reveals a putative signaling dimer.
  J Biol Chem, 283, 11861-11865.
PDB code: 2j67
  18782031 Y.Lai, and R.L.Gallo (2008).
Toll-like receptors in skin infections and inflammatory diseases.
  Infect Disord Drug Targets, 8, 144-155.  
17607319 T.Huyton, J.Rossjohn, and M.Wilce (2007).
Toll-like receptors: structural pieces of a curve-shaped puzzle.
  Immunol Cell Biol, 85, 406-410.  
17667936 T.M.Watters, E.F.Kenny, and L.A.O'Neill (2007).
Structure, function and regulation of the Toll/IL-1 receptor adaptor proteins.
  Immunol Cell Biol, 85, 411-419.  
17665992 V.Y.Toshchakov, and S.N.Vogel (2007).
Cell-penetrating TIR BB loop decoy peptides a novel class of TLR signaling inhibitors and a tool to study topology of TIR-TIR interactions.
  Expert Opin Biol Ther, 7, 1035-1050.  
17331607 W.Low, A.Mortlock, L.Petrovska, T.Dottorini, G.Dougan, and A.Crisanti (2007).
Functional cell permeable motifs within medically relevant proteins.
  J Biotechnol, 129, 555-564.  
17110940 B.J.DeYoung, and R.W.Innes (2006).
Plant NBS-LRR proteins in pathogen sensing and host defense.
  Nat Immunol, 7, 1243-1249.  
17034761 H.S.Youn, J.Y.Lee, S.I.Saitoh, K.Miyake, and D.H.Hwang (2006).
Auranofin, as an anti-rheumatic gold compound, suppresses LPS-induced homodimerization of TLR4.
  Biochem Biophys Res Commun, 350, 866-871.  
16720699 J.K.Bell, J.Askins, P.R.Hall, D.R.Davies, and D.M.Segal (2006).
The dsRNA binding site of human Toll-like receptor 3.
  Proc Natl Acad Sci U S A, 103, 8792-8797.  
16893894 J.K.Gautam, Ashish, L.D.Comeau, J.K.Krueger, and M.F.Smith (2006).
Structural and functional evidence for the role of the TLR2 DD loop in TLR1/TLR2 heterodimerization and signaling.
  J Biol Chem, 281, 30132-30142.  
16917510 N.J.Gay, M.Gangloff, and A.N.Weber (2006).
Toll-like receptors as molecular switches.
  Nat Rev Immunol, 6, 693-698.  
16832055 Z.Jiang, P.Georgel, C.Li, J.Choe, K.Crozat, S.Rutschmann, X.Du, T.Bigby, S.Mudd, S.Sovath, I.A.Wilson, A.Olson, and B.Beutler (2006).
Details of Toll-like receptor:adapter interaction revealed by germ-line mutagenesis.
  Proc Natl Acad Sci U S A, 103, 10961-10966.  
15849357 C.Li, J.Zienkiewicz, and J.Hawiger (2005).
Interactive sites in the MyD88 Toll/interleukin (IL) 1 receptor domain responsible for coupling to the IL1beta signaling pathway.
  J Biol Chem, 280, 26152-26159.  
15123616 J.A.Khan, E.K.Brint, L.A.O'Neill, and L.Tong (2004).
Crystal structure of the Toll/interleukin-1 receptor domain of human IL-1RAPL.
  J Biol Chem, 279, 31664-31670.
PDB code: 1t3g
12888566 A.Dunne, M.Ejdeback, P.L.Ludidi, L.A.O'Neill, and N.J.Gay (2003).
Structural complementarity of Toll/interleukin-1 receptor domains in Toll-like receptors and the adaptors Mal and MyD88.
  J Biol Chem, 278, 41443-41451.  
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.