PDBsum entry 2z81

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Immune system PDB id
Protein chain
549 a.a. *
Waters ×312
* Residue conservation analysis
PDB id:
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.
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
30-Aug-07     Release date:   02-Oct-07    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q9QUN7  (TLR2_MOUSE) -  Toll-like receptor 2
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.
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

  PubMed id Reference
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PDB code: 3rg1
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European wild boars and domestic pigs display different polymorphic patterns in the Toll-like receptor (TLR) 1, TLR2, and TLR6 genes.
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Treating atherosclerosis: the potential of Toll-like receptors as therapeutic targets.
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TollML: a database of toll-like receptor structural motifs.
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Complementary Tolls in the periodontium: how periodontal bacteria modify complement and Toll-like receptor responses to prevail in the host.
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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).
Mass spectrometric-based protein chips for detection of food-derived bioactive components.
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20949035 M.A.Müller-Anstett, P.Müller, T.Albrecht, M.Nega, J.Wagener, Q.Gao, S.Kaesler, M.Schaller, T.Biedermann, and F.Götz (2010).
Staphylococcal peptidoglycan co-localizes with Nod2 and TLR2 and activates innate immune response via both receptors in primary murine keratinocytes.
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Mycobacterium tuberculosis lipoprotein LprG (Rv1411c) binds triacylated glycolipid agonists of Toll-like receptor 2.
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PDB codes: 3mh8 3mh9 3mha
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Structural basis for solute transport, nucleotide regulation, and immunological recognition of Neisseria meningitidis PorB.
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PDB codes: 3a2r 3a2s 3a2t 3a2u 3vzt 3vzu 3vzw
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Current views of toll-like receptor signaling pathways.
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The Staphylococcus aureus lipoprotein SitC colocalizes with Toll-like receptor 2 (TLR2) in murine keratinocytes and elicits intracellular TLR2 accumulation.
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PDB code: 3fxi
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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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Soluble CD36 ectodomain binds negatively charged diacylglycerol ligands and acts as a co-receptor for TLR2.
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20064441 M.Schenk, J.T.Belisle, and R.L.Modlin (2009).
TLR2 looks at lipoproteins.
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Essential Roles of Hydrophobic Residues in Both MD-2 and Toll-like Receptor 4 in Activation by Endotoxin.
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19801985 R.Barbalat, L.Lau, R.M.Locksley, and G.M.Barton (2009).
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19493685 R.I.Tapping (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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19629181 S.A.Benson, and J.D.Ernst (2009).
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19627256 S.Carpenter, and L.A.O'Neill (2009).
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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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19574958 S.Santos-Sierra, S.D.Deshmukh, J.Kalnitski, P.Küenzi, M.P.Wymann, D.T.Golenbock, and P.Henneke (2009).
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19400727 T.Boller, and G.Felix (2009).
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19246554 T.Kawai, and S.Akira (2009).
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19120483 T.P.Monie, M.C.Moncrieffe, and N.J.Gay (2009).
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19835640 W.J.McCormack, A.E.Parker, and L.A.O'Neill (2009).
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Crystallization of Spätzle, a cystine-knot protein involved in embryonic development and innate immunity in Drosophila melanogaster.
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18818359 B.W.Han, B.R.Herrin, M.D.Cooper, and I.A.Wilson (2008).
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PDB code: 3e6j
18227810 F.Leulier, and B.Lemaitre (2008).
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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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18516040 G.Gerold, K.A.Ajaj, M.Bienert, H.J.Laws, A.Zychlinsky, and Diego (2008).
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19077264 H.Park, J.Huxley-Jones, R.P.Boot-Handford, P.N.Bishop, T.K.Attwood, and J.Bella (2008).
LRRCE: a leucine-rich repeat cysteine capping motif unique to the chordate lineage.
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18172197 J.N.Leonard, R.Ghirlando, J.Askins, J.K.Bell, D.H.Margulies, D.R.Davies, and D.M.Segal (2008).
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PDB codes: 3cig 3ciy
18347020 M.Gangloff, A.Murali, J.Xiong, C.J.Arnot, A.N.Weber, A.M.Sandercock, C.V.Robinson, R.Sarisky, A.Holzenburg, C.Kao, and N.J.Gay (2008).
Structural insight into the mechanism of activation of the Toll receptor by the dimeric ligand Spätzle.
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Baseless assumptions: activation of TLR9 by DNA.
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18446235 M.Proell, S.J.Riedl, J.H.Fritz, A.M.Rojas, and R.Schwarzenbacher (2008).
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18468694 M.R.Kimbrell, H.Warshakoon, J.R.Cromer, S.Malladi, J.D.Hood, R.Balakrishna, T.A.Scholdberg, and S.A.David (2008).
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18701082 M.S.Jin, and J.O.Lee (2008).
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Immunogenecity of modified alkane polymers is mediated through TLR1/2 activation.
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18625310 S.Akashi-Takamura, and K.Miyake (2008).
TLR accessory molecules.
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18800365 S.Józefowski, A.Sobota, and K.Kwiatkowska (2008).
How Mycobacterium tuberculosis subverts host immune responses.
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LspA inactivation in Mycobacterium tuberculosis results in attenuation without affecting phagosome maturation arrest.
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18079113 S.Thakran, H.Li, C.L.Lavine, M.A.Miller, J.E.Bina, X.R.Bina, and F.Re (2008).
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18317019 T.Sigsgaard, H.J.Hoffmann, and P.S.Thorne (2008).
The role of innate immunity in occupational allergy: recent findings.
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Pathogen recognition by innate receptors.
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The potential of targeting Toll-like receptor 2 in autoimmune and inflammatory diseases.
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