Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Originally published in Science Express on 16 June 2005
Science 22 July 2005:
Vol. 309. no. 5734, pp. 581 - 585
DOI: 10.1126/science.1115253

Research Articles

Crystal Structure of Human Toll-Like Receptor 3 (TLR3) Ectodomain

Jungwoo Choe, Matthew S. Kelker, Ian A. Wilson*

Toll-like receptors (TLRs) play key roles in activating immune responses during infection. The human TLR3 ectodomain structure at 2.1 angstroms reveals a large horseshoe-shaped solenoid assembled from 23 leucine-rich repeats (LRRs). Asparagines conserved in the 24-residue LRR motif contribute extensive hydrogen-bonding networks for solenoid stabilization. TLR3 is largely masked by carbohydrate, but one face is glycosylation-free, which suggests its potential role in ligand binding and oligomerization. Highly conserved surface residues and a TLR3-specific LRR insertion form a homodimer interface in the crystal, whereas two patches of positively charged residues and a second insertion would provide an appropriate binding site for double-stranded RNA.

Department of Molecular Biology and The Skaggs Institute for Chemical Biology, The Scripps Research Institute (TSRI), 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.

Published online 16 June 2005

Include this information when citing this paper.

* To whom correspondence should be addressed. E-mail: wilson{at}scripps.edu

Read the Full Text



THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
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, and D. R. Davies (2008)
Science 320, 379-381
   Abstract »    Full Text »    PDF »
Toll-like Receptor Polymorphisms and Age-Related Macular Degeneration.
A. O. Edwards, D. Chen, B. L. Fridley, K. M. James, Y. Wu, G. Abecasis, A. Swaroop, M. Othman, K. Branham, S. K. Iyengar, et al. (2008)
Invest. Ophthalmol. Vis. Sci. 49, 1652-1659
   Abstract »    Full Text »    PDF »
The TLR3 signaling complex forms by cooperative receptor dimerization.
J. N. Leonard, R. Ghirlando, J. Askins, J. K. Bell, D. H. Margulies, D. R. Davies, and D. M. Segal (2008)
PNAS 105, 258-263
   Abstract »    Full Text »    PDF »
Sensing of Viral Infection and Activation of Innate Immunity by Toll-Like Receptor 3.
E. Vercammen, J. Staal, and R. Beyaert (2008)
Clin. Microbiol. Rev. 21, 13-25
   Abstract »    Full Text »    PDF »
TLR3 Deficiency in Patients with Herpes Simplex Encephalitis.
S.-Y. Zhang, E. Jouanguy, S. Ugolini, A. Smahi, G. Elain, P. Romero, D. Segal, V. Sancho-Shimizu, L. Lorenzo, A. Puel, et al. (2007)
Science 317, 1522-1527
   Abstract »    Full Text »    PDF »
A Novel Role of the Lumican Core Protein in Bacterial Lipopolysaccharide-induced Innate Immune Response.
F. Wu, N. Vij, L. Roberts, S. Lopez-Briones, S. Joyce, and S. Chakravarti (2007)
J. Biol. Chem. 282, 26409-26417
   Abstract »    Full Text »    PDF »
The Functions of Plant TIR Domains.
T. M. Burch-Smith and S. P. Dinesh-Kumar (2007)
Sci. STKE 2007, pe46
   Abstract »    Full Text »    PDF »
Effects of Single Nucleotide Polymorphisms on Toll-like Receptor 3 Activity and Expression in Cultured Cells.
C. T. Ranjith-Kumar, W. Miller, J. Sun, J. Xiong, J. Santos, I. Yarbrough, R. J. Lamb, J. Mills, K. E. Duffy, S. Hoose, et al. (2007)
J. Biol. Chem. 282, 17696-17705
   Abstract »    Full Text »    PDF »
Toll-like Receptors and Type I Interferons.
S. Uematsu and S. Akira (2007)
J. Biol. Chem. 282, 15319-15323
   Abstract »    Full Text »    PDF »
The Polymorphism P315L of Human Toll-Like Receptor 1 Impairs Innate Immune Sensing of Microbial Cell Wall Components.
K. O. Omueti, D. J. Mazur, K. S. Thompson, E. A. Lyle, and R. I. Tapping (2007)
J. Immunol. 178, 6387-6394
   Abstract »    Full Text »    PDF »
TLR3 Is Essential for the Induction of Protective Immunity against Punta Toro Virus Infection by the Double-Stranded RNA (dsRNA), Poly(I:C12U), but not Poly(I:C): Differential Recognition of Synthetic dsRNA Molecules.
B. B. Gowen, M.-H. Wong, K.-H. Jung, A. B. Sanders, W. M. Mitchell, L. Alexopoulou, R. A. Flavell, and R. W. Sidwell (2007)
J. Immunol. 178, 5200-5208
   Abstract »    Full Text »    PDF »
Evidence for Evolving Toll-IL-1 Receptor-Containing Adaptor Molecule Function in Vertebrates.
C. Sullivan, J. H. Postlethwait, C. R. Lage, P. J. Millard, and C. H. Kim (2007)
J. Immunol. 178, 4517-4527
   Abstract »    Full Text »    PDF »
Biochemical and Functional Analyses of the Human Toll-like Receptor 3 Ectodomain.
C. T. Ranjith-Kumar, W. Miller, J. Xiong, W. K. Russell, R. Lamb, J. Santos, K. E. Duffy, L. Cleveland, M. Park, K. Bhardwaj, et al. (2007)
J. Biol. Chem. 282, 7668-7678
   Abstract »    Full Text »    PDF »
Structural Diversity of the Hagfish Variable Lymphocyte Receptors.
H. M. Kim, S. C. Oh, K. J. Lim, J. Kasamatsu, J. Y. Heo, B. S. Park, H. Lee, O. J. Yoo, M. Kasahara, and J.-O. Lee (2007)
J. Biol. Chem. 282, 6726-6732
   Abstract »    Full Text »    PDF »
A conserved surface on Toll-like receptor 5 recognizes bacterial flagellin.
E. Andersen-Nissen, K. D. Smith, R. Bonneau, R. K. Strong, and A. Aderem (2007)
J. Exp. Med. 204, 393-403
   Abstract »    Full Text »    PDF »
Lamprey TLRs with Properties Distinct from Those of the Variable Lymphocyte Receptors.
A. Ishii, A. Matsuo, H. Sawa, T. Tsujita, K. Shida, M. Matsumoto, and T. Seya (2007)
J. Immunol. 178, 397-406
   Abstract »    Full Text »    PDF »
Toll-like Receptor 4 Region Glu24-Lys47 Is a Site for MD-2 Binding: IMPORTANCE OF CYS29 AND CYS40.
C. Nishitani, H. Mitsuzawa, H. Sano, T. Shimizu, N. Matsushima, and Y. Kuroki (2006)
J. Biol. Chem. 281, 38322-38329
   Abstract »    Full Text »    PDF »
The Structure of the Lingo-1 Ectodomain, a Module Implicated in Central Nervous System Repair Inhibition.
L. Mosyak, A. Wood, B. Dwyer, M. Buddha, M. Johnson, A. Aulabaugh, X. Zhong, E. Presman, S. Benard, K. Kelleher, et al. (2006)
J. Biol. Chem. 281, 36378-36390
   Abstract »    Full Text »    PDF »
Flavivirus Activation of Plasmacytoid Dendritic Cells Delineates Key Elements of TLR7 Signaling beyond Endosomal Recognition.
J. P. Wang, P. Liu, E. Latz, D. T. Golenbock, R. W. Finberg, and D. H. Libraty (2006)
J. Immunol. 177, 7114-7121
   Abstract »    Full Text »    PDF »
TLR9 and the Recognition of Self and Non-Self Nucleic Acids.
M. S LAMPHIER, C. M SIROIS, A. VERMA, D. T GOLENBOCK, and E. LATZ (2006)
Ann. N.Y. Acad. Sci. 1082, 31-43
   Abstract »    Full Text »    PDF »
TLR3 Ligation Activates an Antiviral Response in Human Fetal Astrocytes: A Role for Viperin/cig5.
M. A. Rivieccio, H.-S. Suh, Y. Zhao, M.-L. Zhao, K. C. Chin, S. C. Lee, and C. F. Brosnan (2006)
J. Immunol. 177, 4735-4741
   Abstract »    Full Text »    PDF »
Conserved Features in the Extracellular Domain of Human Toll-like Receptor 8 Are Essential for pH-dependent Signaling.
R. J. Gibbard, P. J. Morley, and N. J. Gay (2006)
J. Biol. Chem. 281, 27503-27511
   Abstract »    Full Text »    PDF »
Invited review: Roles for accessory molecules in microbial recognition by Toll-like receptors.
K. Miyake (2006)
Innate Immunity 12, 195-204
   Abstract »    PDF »
New insights into the regulation of TLR signaling.
S. M. Miggin and L. A. J. O'Neill (2006)
J. Leukoc. Biol. 80, 220-226
   Abstract »    Full Text »    PDF »
Intracellular TLR Signaling: A Structural Perspective on Human Disease.
M. V. Lasker and S. K. Nair (2006)
J. Immunol. 177, 11-16
   Abstract »    Full Text »    PDF »
Analysis of TLR4 Polymorphic Variants: New Insights into TLR4/MD-2/CD14 Stoichiometry, Structure, and Signaling.
P. Rallabhandi, J. Bell, M. S. Boukhvalova, A. Medvedev, E. Lorenz, M. Arditi, V. G. Hemming, J. C. G. Blanco, D. M. Segal, and S. N. Vogel (2006)
J. Immunol. 177, 322-332
   Abstract »    Full Text »    PDF »
The dsRNA binding site of human Toll-like receptor 3.
J. K. Bell, J. Askins, P. R. Hall, D. R. Davies, and D. M. Segal (2006)
PNAS 103, 8792-8797
   Abstract »    Full Text »    PDF »
Kdo2-Lipid A of Escherichia coli, a defined endotoxin that activates macrophages via TLR-4.
C. R. H. Raetz, T. A. Garrett, C. M. Reynolds, W. A. Shaw, J. D. Moore, D. C. Smith Jr., A. A. Ribeiro, R. C. Murphy, R. J. Ulevitch, C. Fearns, et al. (2006)
J. Lipid Res. 47, 1097-1111
   Abstract »    Full Text »    PDF »
Structural and Functional Analyses of the Human Toll-like Receptor 3: ROLE OF GLYCOSYLATION.
J. Sun, K. E. Duffy, C. T. Ranjith-Kumar, J. Xiong, R. J. Lamb, J. Santos, H. Masarapu, M. Cunningham, A. Holzenburg, R. T. Sarisky, et al. (2006)
J. Biol. Chem. 281, 11144-11151
   Abstract »    Full Text »    PDF »
Polyoma Virus-Like Particles Elicit Polarized Cytokine Responses in APCs from Tumor-Susceptible and -Resistant Mice.
P. Velupillai, R. L. Garcea, and T. L. Benjamin (2006)
J. Immunol. 176, 1148-1153
   Abstract »    Full Text »    PDF »
Recognition of Double-stranded RNA by Human Toll-like Receptor 3 and Downstream Receptor Signaling Requires Multimerization and an Acidic pH.
O. de Bouteiller, E. Merck, U. A. Hasan, S. Hubac, B. Benguigui, G. Trinchieri, E. E. M. Bates, and C. Caux (2005)
J. Biol. Chem. 280, 38133-38145
   Abstract »    Full Text »    PDF »
Identification of the Critical Residues Involved in Peptidoglycan Detection by Nod1.
S. E. Girardin, M. Jehanno, D. Mengin-Lecreulx, P. J. Sansonetti, P. M. Alzari, and D. J. Philpott (2005)
J. Biol. Chem. 280, 38648-38656
   Abstract »    Full Text »    PDF »
Domain Exchange between Human Toll-like Receptors 1 and 6 Reveals a Region Required for Lipopeptide Discrimination.
K. O. Omueti, J. M. Beyer, C. M. Johnson, E. A. Lyle, and R. I. Tapping (2005)
J. Biol. Chem. 280, 36616-36625
   Abstract »    Full Text »    PDF »



ADVERTISEMENT
Click Me!

ADVERTISEMENT
Click Me!

To Advertise     Find Products