spacer
spacer

PDBsum entry 3a7c
Go to PDB code: 
protein ligands metals links
Immune system PDB id
3a7c

 

 

 

 

Loading ...

 
JSmol PyMol  
Contents
Protein chain
549 a.a. *
Ligands
NAG-NAG
NAG-NAG-MAN
NAG
PDK
Metals
_LU
Waters ×223
* Residue conservation analysis
PDB id:
3a7c
Name: Immune system
Title: Crystal structure of tlr2-pe-dtpa complex
Structure: Toll-like receptor 2, variable lymphocyte receptor b. Chain: a. Fragment: extracellular domain, unp residues 1-506(mouse), unp residues 133-200(inshore hagfish). Synonym: tlr2, vlrb.61. Engineered: yes
Source: Mus musculus, eptatretus burgeri. Mouse, inshore hagfish. Organism_taxid: 10090, 7764. Gene: tlr2. Expressed in: trichoplusia ni. Expression_system_taxid: 7111.
Resolution:
2.40Å     R-factor:   0.215     R-free:   0.290
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
Date:
20-Sep-09     Release date:   24-Nov-09    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q4G1L2  (Q4G1L2_EPTBU) -  Variable lymphocyte receptor B from Eptatretus burgeri
Seq:
Struc: 		 
Seq:
Struc: 		273 a.a.
549 a.a.*
Protein chain
Pfam   ArchSchema ?
Q9QUN7  (TLR2_MOUSE) -  Toll-like receptor 2 from Mus musculus
Seq:
Struc: 		 
Seq:
Struc: 		784 a.a.
549 a.a.*
Key:    PfamA domain  Secondary structure
* PDB and UniProt seqs differ at 167 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.3.2.2.6  - ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: NAD+ + H2O = ADP-D-ribose + nicotinamide + H+
NAD(+)
 + H2O
 = ADP-D-ribose
 + nicotinamide
 + H(+)
Bound ligand (Het Group name = NAG)
matches with 43.75% similarity
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    reference    
 
 
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.
 
  ABSTRACT  
 
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.

 

spacer
spacer