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PDBsum entry 2z81

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Immune system PDB id
2z81
Jmol
Contents
Protein chain
549 a.a. *
Ligands
NAG-NAG-BMA
NAG-NAG-MAN
NAG
PCJ
Waters ×312
* Residue conservation analysis
PDB id:
2z81
Name: Immune system
Title: Crystal structure of the tlr1-tlr2 heterodimer induced by bi tri-acylated lipopeptide
Structure: Toll-like receptor 2, variable lymphocyte recepto chain: a. Fragment: tlr2, unp residues 27-506(mouse), vlrb.61, unp re 136-199(inshore hagfish). Synonym: cd282 antigen. Engineered: yes
Source: Mus musculus, eptatretus burgeri. House mouse, inshore hagfish. Organism_taxid: 10090,7764. Strain: ,. Gene: tlr2, vlrb. Expressed in: trichoplusia ni. Expression_system_taxid: 7111.
Resolution:
1.80Å     R-factor:   0.213     R-free:   0.232
Authors: J.O.Lee,M.S.Jin,S.E.Kim,J.Y.Heo
Key ref:
M.S.Jin et al. (2007). Crystal Structure of the TLR1-TLR2 Heterodimer Induced by Binding of a Tri-Acylated Lipopeptide. Cell, 130, 1071-1082. PubMed id: 17889651 DOI: 10.1016/j.cell.2007.09.008
Date:
30-Aug-07     Release date:   02-Oct-07    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q9QUN7  (TLR2_MOUSE) -  Toll-like receptor 2
Seq:
Struc:
 
Seq:
Struc:
784 a.a.
549 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 62 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     integral to membrane   1 term 
  Biological process     innate immune response   7 terms 

 

 
DOI no: 10.1016/j.cell.2007.09.008 Cell 130:1071-1082 (2007)
PubMed id: 17889651  
 
 
Crystal Structure of the TLR1-TLR2 Heterodimer Induced by Binding of a Tri-Acylated Lipopeptide.
M.S.Jin, S.E.Kim, J.Y.Heo, M.E.Lee, H.M.Kim, S.G.Paik, H.Lee, J.O.Lee.
 
  ABSTRACT  
 
TLR2 in association with TLR1 or TLR6 plays an important role in the innate immune response by recognizing microbial lipoproteins and lipopeptides. Here we present the crystal structures of the human TLR1-TLR2-lipopeptide complex and of the mouse TLR2-lipopeptide complex. Binding of the tri-acylated lipopeptide, Pam(3)CSK(4), induced the formation of an "m" shaped heterodimer of the TLR1 and TLR2 ectodomains whereas binding of the di-acylated lipopeptide, Pam(2)CSK(4), did not. The three lipid chains of Pam(3)CSK(4) mediate the heterodimerization of the receptor; the two ester-bound lipid chains are inserted into a pocket in TLR2, while the amide-bound lipid chain is inserted into a hydrophobic channel in TLR1. An extensive hydrogen-bonding network, as well as hydrophobic interactions, between TLR1 and TLR2 further stabilize the heterodimer. We propose that formation of the TLR1-TLR2 heterodimer brings the intracellular TIR domains close to each other to promote dimerization and initiate signaling.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. Crystallized TLR-VLR Hybrid Proteins
Full-length and VLR hybrids of TLR1 (A) and TLR2 (B) are represented schematically. TLR1 and TLR2 and hagfish VLRB.61 are shown in green, blue, and white boxes, respectively. The ligand-binding and dimerization domains were identified from our crystal structure. Amino acid sequences at the fusion boundaries and the corresponding conserved patterns are given underneath the boxes. The sequences within the parentheses are non-native sequences from the cloning sites.
Figure 4.
Figure 4. The Lipopeptide-Binding Site of the Human TLR1-TLR2 Complex
(A) TLR1 and TLR2 residues involved in Pam[3]CSK[4] binding are drawn in green and blue, respectively. The hydrogen bonds are shown by broken red lines. Carbons, nitrogens, oxygens, and a sulfur of the Pam[3]CSK[4] are colored in orange, blue, red, and green, respectively. The H3 helix is drawn as a coil for clarity. I319' of TLR1 is hidden behind the H3′ helix.
(B) Chemical structure of Pam[3]CSK[4.] Residues interacting with Pam[3]CSK[4] are labeled. Hydrogen bonds are drawn with broken red lines.
(C) The shape of the Pam[3]CSK[4]-binding pocket is shown in mesh. Molecular surfaces that belong to TLR1 and TLR2 are drawn in green and blue, respectively. Pam[3]CSK[4] is shown as a space-filling model.
 
  The above figures are reprinted by permission from Cell Press: Cell (2007, 130, 1071-1082) copyright 2007.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

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PDB code: 3rg1
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PDB code: 3k2d
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A five-amino-acid motif in the undefined region of the TLR8 ectodomain is required for species-specific ligand recognition.
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20388144 J.Stagsted, A.L.Jørgensen, and H.R.Juul-Madsen (2010).
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  Ann N Y Acad Sci, 1190, 133-140.  
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The peptide sequence of diacyl lipopeptides determines dendritic cell TLR2-mediated NK activation.
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Advances in the design and delivery of peptide subunit vaccines with a focus on toll-like receptor agonists.
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PDB codes: 3mh8 3mh9 3mha
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PDB codes: 3a2r 3a2s 3a2t 3a2u 3vzt 3vzu 3vzw
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Structural requirement for the agonist activity of the TLR2 ligand Pam2Cys.
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PDB code: 3fxi
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The toll-like receptor 3:dsRNA signaling complex.
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Mincle is a long sought receptor for mycobacterial cord factor.
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Recognition of lipopeptide patterns by Toll-like receptor 2-Toll-like receptor 6 heterodimer.
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PDB codes: 3a79 3a7b 3a7c
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19847289 M.J.Jimenez-Dalmaroni, N.Xiao, A.L.Corper, P.Verdino, G.D.Ainge, D.S.Larsen, G.F.Painter, P.M.Rudd, R.A.Dwek, K.Hoebe, B.Beutler, and I.A.Wilson (2009).
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19691556 R.N.Coler, D.Carter, M.Friede, and S.G.Reed (2009).
Adjuvants for malaria vaccines.
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19103770 S.Ji, J.E.Shin, Y.S.Kim, J.E.Oh, B.M.Min, and Y.Choi (2009).
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19234193 S.Liang, K.B.Hosur, S.Lu, H.F.Nawar, B.R.Weber, R.I.Tapping, T.D.Connell, and G.Hajishengallis (2009).
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PDB code: 3e6j
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18549457 G.Ferwerda, F.Meyer-Wentrup, B.J.Kullberg, M.G.Netea, and G.J.Adema (2008).
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PDB codes: 3cig 3ciy
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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.