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PDBsum entry 3cig
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Immune system PDB id
3cig

 

 

 

 

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JSmol PyMol  
Contents
Protein chain
663 a.a. *
Ligands
NAG-NDG ×2
NAG-NAG-FUL
NAG-NAG ×2
NAG-NDG-MAN-BMA-
MAN
NAG-NDG-BMA-FUL
NAG ×4
FUC
Waters ×79
* Residue conservation analysis
PDB id:
3cig
Name: Immune system
Title: Crystal structure of mouse tlr3 ectodomain
Structure: Toll-like receptor 3. Chain: a. Fragment: mouse tlr3 ectodomain (unp residues 28-704). Synonym: cd283 antigen. Engineered: yes
Source: Mus musculus. House mouse. Organism_taxid: 10090. Gene: tlr3. Expressed in: trichoplusia ni. Expression_system_taxid: 7111.
Resolution:
2.66Å     R-factor:   0.245     R-free:   0.272
Authors: L.Liu,I.Botos,Y.Wang,J.N.Leonard,J.Shiloach,D.M.Segal,D.R.Davies
Key ref:
L.Liu et al. (2008). Structural basis of toll-like receptor 3 signaling with double-stranded RNA. Science, 320, 379-381. PubMed id: 18420935 DOI: 10.1126/science.1155406
Date:
11-Mar-08     Release date:   06-May-08    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q99MB1  (TLR3_MOUSE) -  Toll-like receptor 3 from Mus musculus
Seq:
Struc: 		 
Seq:
Struc: 		905 a.a.
663 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 

 
DOI no: 10.1126/science.1155406 Science 320:379-381 (2008)
PubMed id: 18420935  
 
 
Structural basis of toll-like receptor 3 signaling with double-stranded RNA.
L.Liu, I.Botos, Y.Wang, J.N.Leonard, J.Shiloach, D.M.Segal, D.R.Davies.
 
  ABSTRACT  
 
Toll-like receptor 3 (TLR3) recognizes double-stranded RNA (dsRNA), a molecular signature of most viruses, and triggers inflammatory responses that prevent viral spread. TLR3 ectodomains (ECDs) dimerize on oligonucleotides of at least 40 to 50 base pairs in length, the minimal length required for signal transduction. To establish the molecular basis for ligand binding and signaling, we determined the crystal structure of a complex between two mouse TLR3-ECDs and dsRNA at 3.4 angstrom resolution. Each TLR3-ECD binds dsRNA at two sites located at opposite ends of the TLR3 horseshoe, and an intermolecular contact between the two TLR3-ECD C-terminal domains coordinates and stabilizes the dimer. This juxtaposition could mediate downstream signaling by dimerizing the cytoplasmic Toll interleukin-1 receptor (TIR) domains. The overall shape of the TLR3-ECD does not change upon binding to dsRNA.
 
  Selected figure(s)  
 
Figure 1.
Fig. 1. dsRNA:TLR3 signaling complex. Mouse TLR3 ectodomains (green and cyan) form a dimer on the dsRNA (blue and red). The N glycans are shown (light green and light blue). (A) The N-and C-terminal binding sites. (B) Illustration of how the two C-terminal domains are brought together in the complex. Figures generated with PyMol (DeLano Scientific, San Carlos, CA). 		Figure 3.
Fig. 3. Closeup of the C-terminal domain interacting residues. Some of these residues (678 to 681) are located on a conserved loop observed in other TLR structures.
 
  The above figures are reprinted from an Open Access publication published by the AAAs: Science (2008, 320, 379-381) copyright 2008.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
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21481769 I.Botos, D.M.Segal, and D.R.Davies (2011).
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21198355 J.J.Khoo, S.Forster, and A.Mansell (2011).
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Structural insight into brassinosteroid perception by BRI1.
  Nature, 474, 472-476.
PDB codes: 3rgx 3rgz
21115235 K.J.McKelvey, J.Highton, and P.A.Hessian (2011).
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PDB codes: 3riz 3rj0
21383168 M.R.de Zoete, L.I.Bouwman, A.M.Keestra, and J.P.van Putten (2011).
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PDB codes: 3rw6 3rw7
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  Annu Rev Immunol, 29, 185-214.  
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Toll-like receptor modulators: a patent review (2006 - 2010).
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Nucleic acid recognition by Toll-like receptors is coupled to stepwise processing by cathepsins and asparagine endopeptidase.
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21857663 S.I.Yoon, M.Hong, and I.A.Wilson (2011).
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PDB code: 3rg1
20953632 T.J.Coffey, and D.Werling (2011).
Therapeutic targeting of the innate immune system in domestic animals.
  Cell Tissue Res, 343, 251-261.  
20352268 T.Wei, J.Gong, S.C.Rössle, F.Jamitzky, W.M.Heckl, and R.W.Stark (2011).
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  J Mol Model, 17, 27-36.  
21254877 U.Holtick, M.E.Scheulen, M.S.von Bergwelt-Baildon, and M.R.Weihrauch (2011).
Toll-like receptor 9 agonists as cancer therapeutics.
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Toll-like receptors and their adapter molecules.
  Biochemistry (Mosc), 75, 1098-1114.  
20346772 A.L.Blasius, and B.Beutler (2010).
Intracellular toll-like receptors.
  Immunity, 32, 305-315.  
  20706656 A.M.Piccinini, and K.S.Midwood (2010).
DAMPening inflammation by modulating TLR signalling.
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  20073080 A.V.Kubarenko, S.Ranjan, E.Colak, J.George, M.Frank, and A.N.Weber (2010).
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Comparative overview of toll-like receptors in lower animals.
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TollML: a database of toll-like receptor structural motifs.
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Toll-like receptors in innate immunity and infectious diseases.
  Front Med China, 4, 385-393.  
20351243 M.Tanabe, C.M.Nimigean, and T.M.Iverson (2010).
Structural basis for solute transport, nucleotide regulation, and immunological recognition of Neisseria meningitidis PorB.
  Proc Natl Acad Sci U S A, 107, 6811-6816.
PDB codes: 3a2r 3a2s 3a2t 3a2u 3vzt 3vzu 3vzw
20041442 M.Yoneyama, and T.Fujita (2010).
Recognition of viral nucleic acids in innate immunity.
  Rev Med Virol, 20, 4.  
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.  
20360967 S.J.DeWitte-Orr, S.E.Collins, C.M.Bauer, D.M.Bowdish, and K.L.Mossman (2010).
An accessory to the 'Trinity': SR-As are essential pathogen sensors of extracellular dsRNA, mediating entry and leading to subsequent type I IFN responses.
  PLoS Pathog, 6, e1000829.  
21078117 S.Samuel-Abraham, and J.N.Leonard (2010).
Staying on message: design principles for controlling nonspecific responses to siRNA.
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Structural and functional insights into 5'-ppp RNA pattern recognition by the innate immune receptor RIG-I.
  Nat Struct Mol Biol, 17, 781-787.
PDB code: 3ncu
20593217 Z.L.Chang (2010).
Important aspects of Toll-like receptors, ligands and their signaling pathways.
  Inflamm Res, 59, 791-808.  
19302269 A.Chaturvedi, and S.K.Pierce (2009).
How location governs toll-like receptor signaling.
  Traffic, 10, 621-628.  
19120489 B.Beutler (2009).
Microbe sensing, positive feedback loops, and the pathogenesis of inflammatory diseases.
  Immunol Rev, 227, 248-263.  
19252480 B.S.Park, D.H.Song, H.M.Kim, B.S.Choi, H.Lee, and J.O.Lee (2009).
The structural basis of lipopolysaccharide recognition by the TLR4-MD-2 complex.
  Nature, 458, 1191-1195.
PDB code: 3fxi
19019822 C.T.Ranjith-Kumar, A.Murali, W.Dong, D.Srisathiyanarayanan, R.Vaughan, J.Ortiz-Alacantara, K.Bhardwaj, X.Li, P.Li, and C.C.Kao (2009).
Agonist and antagonist recognition by RIG-I, a cytoplasmic innate immunity receptor.
  J Biol Chem, 284, 1155-1165.  
19120490 D.E.Zak, and A.Aderem (2009).
Systems biology of innate immunity.
  Immunol Rev, 227, 264-282.  
19176317 D.Piccioli, C.Sammicheli, S.Tavarini, S.Nuti, E.Frigimelica, A.G.Manetti, A.Nuccitelli, S.Aprea, S.Valentini, E.Borgogni, A.Wack, and N.M.Valiante (2009).
Human plasmacytoid dendritic cells are unresponsive to bacterial stimulation and require a novel type of cooperation with myeloid dendritic cells for maturation.
  Blood, 113, 4232-4239.  
19508916 D.T.O'Hagan, and E.De Gregorio (2009).
The path to a successful vaccine adjuvant--'the long and winding road'.
  Drug Discov Today, 14, 541-551.  
19211304 D.Werling, O.C.Jann, V.Offord, E.J.Glass, and T.J.Coffey (2009).
Variation matters: TLR structure and species-specific pathogen recognition.
  Trends Immunol, 30, 124-130.  
19302040 F.Martinon, A.Mayor, and J.Tschopp (2009).
The inflammasomes: guardians of the body.
  Annu Rev Immunol, 27, 229-265.  
19556980 G.M.Barton, and J.C.Kagan (2009).
A cell biological view of Toll-like receptor function: regulation through compartmentalization.
  Nat Rev Immunol, 9, 535-542.  
19382893 H.Kumar, T.Kawai, and S.Akira (2009).
Pathogen recognition in the innate immune response.
  Biochem J, 420, 1.  
19174176 H.Wagner (2009).
The immunogenicity of CpG-antigen conjugates.
  Adv Drug Deliv Rev, 61, 243-247.  
19595807 I.Botos, L.Liu, Y.Wang, D.M.Segal, and D.R.Davies (2009).
The toll-like receptor 3:dsRNA signaling complex.
  Biochim Biophys Acta, 1789, 667-674.  
19211030 J.Vollmer, and A.M.Krieg (2009).
Immunotherapeutic applications of CpG oligodeoxynucleotide TLR9 agonists.
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19931471 J.Y.Kang, X.Nan, M.S.Jin, S.J.Youn, Y.H.Ryu, S.Mah, S.H.Han, H.Lee, S.G.Paik, and J.O.Lee (2009).
Recognition of lipopeptide patterns by Toll-like receptor 2-Toll-like receptor 6 heterodimer.
  Immunity, 31, 873-884.
PDB codes: 3a79 3a7b 3a7c
19559490 K.Chen, J.Huang, Y.Liu, W.Gong, Y.Cui, and J.M.Wang (2009).
Synergy of TRIF-dependent TLR3 and MyD88-dependent TLR7 in up-regulating expression of mouse FPR2, a promiscuous G-protein-coupled receptor, in microglial cells.
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19352178 K.D.Smith (2009).
Toll-like receptors in kidney disease.
  Curr Opin Nephrol Hypertens, 18, 189-196.  
19474110 L.A.O'Neill, C.E.Bryant, and S.L.Doyle (2009).
Therapeutic targeting of Toll-like receptors for infectious and inflammatory diseases and cancer.
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19252739 M.Helmy, J.Gohda, J.Inoue, M.Tomita, M.Tsuchiya, and K.Selvarajoo (2009).
Predicting novel features of toll-like receptor 3 signaling in macrophages.
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19016785 M.Padmanabhan, P.Cournoyer, and S.P.Dinesh-Kumar (2009).
The leucine-rich repeat domain in plant innate immunity: a wealth of possibilities.
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19321453 N.Resman, J.Vasl, A.Oblak, P.Pristovsek, T.L.Gioannini, J.P.Weiss, and R.Jerala (2009).
Essential roles of hydrophobic residues in both MD-2 and toll-like receptor 4 in activation by endotoxin.
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19651780 N.Sasaki, M.Ogasawara, T.Sekiguchi, S.Kusumoto, and H.Satake (2009).
Toll-like receptors of the ascidian Ciona intestinalis: prototypes with hybrid functionalities of vertebrate Toll-like receptors.
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19625408 N.Wang, Y.Liang, S.Devaraj, J.Wang, S.M.Lemon, and K.Li (2009).
Toll-like receptor 3 mediates establishment of an antiviral state against hepatitis C virus in hepatoma cells.
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19120477 O.Takeuchi, and S.Akira (2009).
Innate immunity to virus infection.
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Innate immune sensing and activation of cell surface Toll-like receptors.
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RNAi nanoparticles in the service of personalized medicine.
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Adjuvants for malaria vaccines.
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PDB code: 3eqt
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PDB code: 3e6j
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TLR accessory molecules.
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The ectodomain of Toll-like receptor 9 is cleaved to generate a functional receptor.
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  19017955 S.M.Ngoi, M.G.Tovey, and A.T.Vella (2008).
Targeting poly(I:C) to the TLR3-independent pathway boosts effector CD8 T cell differentiation through IFN-alpha/beta.
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18986514 T.Wei, J.Gong, F.Jamitzky, W.M.Heckl, R.W.Stark, and S.C.Roessle (2008).
LRRML: a conformational database and an XML description of leucine-rich repeats (LRRs).
  BMC Struct Biol, 8, 47.  
18652893 W.Barchet, V.Wimmenauer, M.Schlee, and G.Hartmann (2008).
Accessing the therapeutic potential of immunostimulatory nucleic acids.
  Curr Opin Immunol, 20, 389-395.  
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 codes are shown on the right.

 

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