PDBsum entry 3a79

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Immune system PDB id
Protein chains
550 a.a. *
525 a.a. *
NAG ×5
* Residue conservation analysis
PDB id:
Name: Immune system
Title: Crystal structure of tlr2-tlr6-pam2csk4 complex
Structure: Toll-like receptor 2, variable lymphocyte recepto chain: a. Fragment: extracellular domain, unp residues 1-506(mouse), residues 133-200(inshore hagfish). Synonym: tlr2, vlrb.61. Engineered: yes. Toll-like receptor 6, variable lymphocyte recepto chain: b. Fragment: extracellular domain, unp residues 1-482(mouse),
Source: Mus musculus, eptatretus burgeri. Mouse, inshore hagfish. Organism_taxid: 10090, 7764. Gene: tlr2. Expressed in: trichoplusia ni. Expression_system_taxid: 7111. Gene: tlr6. Synthetic: yes. Other_details: synthetic peptide
2.90Å     R-factor:   0.215     R-free:   0.280
Authors: J.Y.Kang,M.S.Jin,J.-O.Lee
Key ref: J.Y.Kang et al. (2009). Recognition of lipopeptide patterns by Toll-like receptor 2-Toll-like receptor 6 heterodimer. Immunity, 31, 873-884. PubMed id: 19931471
20-Sep-09     Release date:   24-Nov-09    
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Protein chain
Pfam   ArchSchema ?
Q4G1L2  (Q4G1L2_EPTBU) -  Variable lymphocyte receptor B
273 a.a.
550 a.a.*
Protein chain
Pfam   ArchSchema ?
Q9QUN7  (TLR2_MOUSE) -  Toll-like receptor 2
784 a.a.
550 a.a.*
Protein chain
Pfam   ArchSchema ?
Q4G1L3  (Q4G1L3_EPTBU) -  Variable lymphocyte receptor B
305 a.a.
525 a.a.*
Protein chain
Pfam   ArchSchema ?
Q9EPW9  (TLR6_MOUSE) -  Toll-like receptor 6
795 a.a.
525 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 336 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     integral to membrane   1 term 
  Biological process     innate immune response   11 terms 
  Biochemical function     transmembrane signaling receptor activity     1 term  


Immunity 31:873-884 (2009)
PubMed id: 19931471  
Recognition of lipopeptide patterns by Toll-like receptor 2-Toll-like receptor 6 heterodimer.
J.Y.Kang, X.Nan, M.S.Jin, S.J.Youn, Y.H.Ryu, S.Mah, S.H.Han, H.Lee, S.G.Paik, J.O.Lee.
Toll-like receptor 2 (TLR2) initiates potent immune responses by recognizing diacylated and triacylated lipopeptides. Its ligand specificity is controlled by whether it heterodimerizes with TLR1 or TLR6. We have determined the crystal structures of TLR2-TLR6-diacylated lipopeptide, TLR2-lipoteichoic acid, and TLR2-PE-DTPA complexes. PE-DTPA, 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-diethylenetriaminepentaacetic acid, is a synthetic phospholipid derivative. Two major factors contribute to the ligand specificity of TLR2-TLR1 or TLR2-TLR6 heterodimers. First, the lipid channel of TLR6 is blocked by two phenylalanines. Simultaneous mutation of these phenylalanines made TLR2-TLR6 fully responsive not only to diacylated but also to triacylated lipopeptides. Second, the hydrophobic dimerization interface of TLR2-TLR6 is increased by 80%, which compensates for the lack of amide lipid interaction between the lipopeptide and TLR2-TLR6. The structures of the TLR2-lipoteichoic acid and the TLR2-PE-DTPA complexes demonstrate that a precise interaction pattern of the head group is essential for a robust immune response by TLR2 heterodimers.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21219575 G.Lal, N.Yin, J.Xu, M.Lin, S.Schroppel, Y.Ding, I.Marie, D.E.Levy, and J.S.Bromberg (2011).
Distinct inflammatory signals have physiologically divergent effects on epigenetic regulation of foxp3 expression and treg function.
  Am J Transplant, 11, 203-214.  
21481769 I.Botos, D.M.Segal, and D.R.Davies (2011).
The structural biology of Toll-like receptors.
  Structure, 19, 447-459.  
21198355 J.J.Khoo, S.Forster, and A.Mansell (2011).
Toll-like receptors as interferon-regulated genes and their role in disease.
  J Interferon Cytokine Res, 31, 13-25.  
21443860 K.S.Jang, J.E.Baik, S.H.Han, D.K.Chung, and B.G.Kim (2011).
Multi-spectrometric analyses of lipoteichoic acids isolated from Lactobacillus plantarum.
  Biochem Biophys Res Commun, 407, 823-830.  
21327200 R.R.Schmidt, C.M.Pedersen, Y.Qiao, and U.Zähringer (2011).
Chemical synthesis of bacterial lipoteichoic acids: an insight on its biological significance.
  Org Biomol Chem, 9, 2040-2052.  
21857663 S.I.Yoon, M.Hong, and I.A.Wilson (2011).
An unusual dimeric structure and assembly for TLR4 regulator RP105-MD-1.
  Nat Struct Mol Biol, 18, 1028-1035.
PDB code: 3rg1
20821040 W.Y.Sheng, and L.Huang (2011).
Cancer immunotherapy and nanomedicine.
  Pharm Res, 28, 200-214.  
20731672 I.J.Claes, S.Lebeer, C.Shen, T.L.Verhoeven, E.Dilissen, G.De Hertogh, D.M.Bullens, J.L.Ceuppens, G.Van Assche, S.Vermeire, P.Rutgeerts, J.Vanderleyden, and S.C.De Keersmaecker (2010).
Impact of lipoteichoic acid modification on the performance of the probiotic Lactobacillus rhamnosus GG in experimental colitis.
  Clin Exp Immunol, 162, 306-314.  
20694006 M.G.Drage, H.C.Tsai, N.D.Pecora, T.Y.Cheng, A.R.Arida, S.Shukla, R.E.Rojas, C.Seshadri, D.B.Moody, W.H.Boom, J.C.Sacchettini, and C.V.Harding (2010).
Mycobacterium tuberculosis lipoprotein LprG (Rv1411c) binds triacylated glycolipid agonists of Toll-like receptor 2.
  Nat Struct Mol Biol, 17, 1088-1095.
PDB codes: 3mh8 3mh9 3mha
21197425 M.Yamamoto, and K.Takeda (2010).
Current views of toll-like receptor signaling pathways.
  Gastroenterol Res Pract, 2010, 240365.  
20574522 O.Renaudet, G.Dasgupta, I.Bettahi, A.Shi, A.B.Nesburn, P.Dumy, and L.BenMohamed (2010).
Linear and branched glyco-lipopeptide vaccines follow distinct cross-presentation pathways and generate different magnitudes of antitumor immunity.
  PLoS One, 5, e11216.  
20877634 R.G.Govindaraj, B.Manavalan, G.Lee, and S.Choi (2010).
Molecular modeling-based evaluation of hTLR10 and identification of potential ligands in Toll-like receptor signaling.
  PLoS One, 5, e12713.  
20846396 S.Bas, R.W.James, and C.Gabay (2010).
Serum lipoproteins attenuate macrophage activation and Toll-Like Receptor stimulation by bacterial lipoproteins.
  BMC Immunol, 11, 46.  
20404851 T.Kawai, and S.Akira (2010).
The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors.
  Nat Immunol, 11, 373-384.  
20584977 Y.H.Wang, J.Jiang, Q.Zhu, A.Z.AlAnezi, R.B.Clark, X.Jiang, D.W.Rowe, and F.C.Nichols (2010).
Porphyromonas gingivalis lipids inhibit osteoblastic differentiation and function.
  Infect Immun, 78, 3726-3735.  
20064441 M.Schenk, J.T.Belisle, and R.L.Modlin (2009).
TLR2 looks at lipoproteins.
  Immunity, 31, 847-849.  
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.