Toll-like receptors as molecular switches

Nature Reviews Immunology

Volumn 6, Issue 9, 2006, Pages 693-698

  Gay, Nicholas J ^a   Gangloff, Monique ^a   Weber, Alexander N R ^b  

^a UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^b GERMAN CANCER RESEARCH CENTER DKFZ   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

TOLL LIKE RECEPTOR; TOLL LIKE RECEPTOR 3;

AMINO ACID SEQUENCE; CELLULAR DISTRIBUTION; CROSS LINKING; CYTOPLASM; DIMERIZATION; HUMAN; LIGAND BINDING; MOLECULAR RECOGNITION; NONHUMAN; PRIORITY JOURNAL; PROTEIN CONFORMATION; PROTEIN DOMAIN; PROTEIN INTERACTION; PROTEIN STRUCTURE; REVIEW; SIGNAL TRANSDUCTION; X RAY CRYSTALLOGRAPHY;

ANIMALS; HUMANS; LIGANDS; MODELS, MOLECULAR; PROTEIN BINDING; SIGNAL TRANSDUCTION; TOLL-LIKE RECEPTORS;

EID: 33748090945     PISSN: 14741733     EISSN: None     Source Type: Journal    
DOI: 10.1038/nri1916     Document Type: Review

References (51)

1. Belvin, M. P. & Anderson, K. V. A conserved signaling pathway: the Drosophila Toll-Dorsal pathway. Annu. Rev. Cell Dev. Biol. 12, 393-416 (1996).
2. Akira, S. & Takeda, K. Toll-like receptor signalling. Nature Rev. Immunol. 4, 499-511 (2004).
3. Iwasaki, A. & Medzhitov, R. Toll-like receptor control of the adaptive immune responses. Nature Immunol. 5, 987-995 (2004).
4. Beutler, B. & Poltorak, A. Sepsis and evolution of the innate immune response. Crit. Care Med. 29, S2-S6; discussion S6-S7 (2001).
5. Rock, F. L., Hardiman, G., Timans, J. C., Kastelein, R. A. & Bazan, J. F. A family of human receptors structurally related to Drosophila Toll. Proc. Natl Acad. Sci. USA 95, 588-593 (1998).
6. Buchanan, S. G. S. & Gay, N. J. Structural and functional diversity in the leucine rich repeat family of proteins. Prog. Biophys. Mol. Biol. 65, 1-44 (1996).
7. Fan, Q. R. & Hendrickson, W. A. Structure of human follicle-stimulating hormone in complex with its receptor. Nature 433, 269-277 (2005).
8. Schimmele, B. & Pluckthun, A. Identification of a functional epitope of the Nogo receptor by a combinatorial approach using ribosome display. J. Mol. Biol. 352, 229-241 (2005).
9. Alder, M. N. et al. Diversity and function of adaptive immune receptors in a jawless vertebrate. Science 310, 1970-1973 (2005).
10. Weber, A. et al. Binding of the Drosophila cytokine Spätzle to Toll is direct and establishes signaling. Nature Immunol. 4, 794-800 (2003).
11. Nagai, Y. et al. Essential role of MD-2 in LPS responsiveness and TLR4 distribution. Nature Immunol. 3, 667-672 (2002).
12. Inohara, N. & Nunez, G. ML - a conserved domain involved in innate immunity and lipid metabolism. Trends Biochem. Sci. 27, 219-221 (2002).
13. Gangloff, M. & Gay, N. J. MD-2: the Toll 'gatekeeper' in endotoxin signalling. Trends Biochem. Sci. 29, 294-300 (2004).
14. Hailman, E. et al. Lipopolysaccharide (LPS)-binding protein accelerates the binding of LPS to CD14. J. Exp. Med. 179, 269-277 (1994).
15. Weber, A. N., Moncrieffe, M. C., Gangloff, M., Imler, J. L. & Gay, N. J. Ligand-receptor and receptor-receptor interactions act in concert to activate signaling in the Drosophila Toll pathway. J. Biol. Chem. 280, 22793-22799 (2005).
16. Winans, K. A. & Hashimoto, C. Ventralization of the Drosophila embryo by deletion of extracellular leucine-rich repeats in the Toll protein. Mol. Biol. Cell 6, 587-596 (1995).
17. Medzhitov, R., Preston-Hurlburt, P. & Janeway, C. A. Jr. A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 388, 394-397 (1997).
18. Schneider, D. S., Hudson, K. L., Lin, T. Y. & Anderson, K. V. Dominant and recessive mutations define functional domains of Toll, a transmembrane protein required for dorsal ventral polarity in the Drosophila embryo. Genes Dev. 5, 797-807 (1991).
19. Hu, X., Yagi, Y., Tanji, T., Zhou, S. & Ip, Y. T. Multimerization and interaction of Toll and Spätzle in Drosophila. Proc. Natl Acad. Sci. USA 101, 9369-9374 (2004).
20. Shimazu, R. et al. MD-2, a molecule that confers lipopolysaccharide responsiveness on Toll-like receptor 4. J. Exp. Med. 189, 1777-1782 (1999).
21. Matsumoto, M., Kikkawa, S., Kohase, M., Miyake, K. & Seya, T. Establishment of a monoclonal antibody against human Toll-like receptor 3 that blocks double-stranded RNA-mediated signaling. Biochem. Biophys. Res. Commun. 293, 1364-1369 (2002).
22. Koshland, D. E. Jr. The structural basis of negative cooperativity: receptors and enzymes. Curr. Opin. Struct. Biol. 6, 757-761 (1996).
23. Urizar, E. et al. Glycoprotein hormone receptors: link between receptor homodimerization and negative cooperativity. EMBO J. 24, 1954-1964 (2005).
24. He, X. L. & Garcia, K. C. Structure of nerve growth factor complexed with the shared neurotrophin receptor p75. Science 304, 870-875 (2004).
25. Bell, J. K. et al. The molecular structure of the Toll-like receptor 3 ligand-binding domain. Proc. Natl Acad. Sci. USA 102, 10976-10980 (2005).
26. Choe, J., Kelker, M. S. & Wilson, I. A. Crystal structure of human Toll-like receptor 3 (TLR3) ectodomain. Science 309, 581-585 (2005).
27. Kirk, P. & Bazan, J. F. Pathogen recognition: TLRs throw us a curve. Immunity 23, 347-350 (2005).
28. Bell, J. K., Askins, J., Hall, P. R., Davies, D. R. & Segal, D. M. The dsRNA binding site of human Toll-like receptor 3. Proc. Natl Acad. Sci. USA 103, 8792-8797 (2006).
29. O'Neill, L. A. J., Fitzgerald, K. A. & Bowie, A. G. The Toll-IL-1 receptor adaptor family grows to five members. Trends Immunol. 24, 286-290 (2003).
30. Xu, Y. W. et al. Structural basis for signal transduction by the Toll/interleukin-1 receptor domains. Nature 408, 111-115 (2000).
31. Dunne, A., Ejdeback, M., Ludidi, P., O'Neill, L. A. J. & Gay, N. J. Structural complementarity of Toll/ interleukin-1 receptor identity regions in Toll-like receptors and the adaptors Mal and MyD88. J. Biol. Chem. 278, 41443-41451 (2003).
32. Fitzgerald, K. A. et al. LPS-TLR4 signaling to IRF-3/7 and NF-κB involves the Toll adapters TRAM and TRIF. J. Exp. Med. 198, 1043-1055 (2003).
33. Lu, X., Gross, A. W. & Lodish, H. F. Active conformation of the erythropoietin receptor: random and cysteine-scanning mutagenesis of the extracellular juxtamembrane and transmembrane domains. J. Biol. Chem. 281, 7002-7011 (2006).
34. Poltorak, A. et al. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 282, 2085-2088 (1998).
35. Tao, X., Xu, Y. W., Zheng, Y., Beg, A. A. & Tong, L. An extensively associated dimer in the structure of the C713S mutant of the TIR domain of human TLR2. Biochem. Biophys. Res. Commun. 299, 216-221 (2002).
36. Ronni, T. et al. Common interaction surfaces of the Toll-like receptor 4 cytoplasmic domain stimulate multiple nuclear targets. Mol. Cell. Biol. 23, 2543-2555 (2003).
37. Gioannini, T. L. et al. Isolation of an endotoxin-MD-2 complex that produces Toll-like receptor 4-dependent cell activation at picomolar concentrations. Proc. Natl Acad. Sci. USA 101, 4186-4191 (2004).
38. Alexopoulou, L., Holt, A. C., Medzhitov, R. & Flavell, R. A. Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3. Nature 413, 732-738 (2001).
39. Bauer, S. et al. Human TLR9 confers responsiveness to bacterial DNA via species-specific CpG motif recognition. Proc. Natl Acad. Sci. USA 98, 9237-9242 (2001).
40. Diebold, S. S., Kaisho, T., Hemmi, H., Akira, S. & Reis e Sousa, C. Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA. Science 303, 1529-1531 (2004).
41. Hemmi, H. et al. Small anti-viral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway. Nature Immunol. 3, 196-200 (2002).
42. Bell, J. K. et al. Leucine-rich repeats and pathogen recognition in Toll-like receptors. Trends Immunol. 24, 528-533 (2003).
43. Gibbard, R. J., Morley, P. J. & Gay, N. J. Conserved features in the extracellular domain of human Toll-like receptor 8 are essential for pH dependent signalling. J. Biol. Chem. 20 July 2006 (doi:10.1074/jbc.M605003200).
44. Latz, E. et al. TLR9 signals after translocating from the ER to CpG DNA in the lysosome. Nature Immunol. 5, 190-198 (2004).
45. Lee, J. et al. Molecular basis for the immunostimulatory activity of guanine nucleoside analogs: activation of Toll-like receptor 7. Proc. Natl Acad. Sci. USA 100, 6646-6651 (2003).
46. Barton, G. M., Kagan, J. C. & Medzhitov, R. Intracellular localization of Toll-like receptor 9 prevents recognition of self DNA but facilitates access to viral DNA. Nature Immunol. 7, 49-56 (2006).
47. Husebye, H. et al. Endocytic pathways regulate Toll-like receptor 4 signaling and link innate and adaptive immunity. EMBO J. 25, 683-692 (2006).
48. Schlessinger, J. Ligand-induced, receptor-mediated dimerization and activation of EGF receptor. Cell 110, 669-672 (2002).
49. Cho, H. S. et al. Structure of the extracellular region of HER2 alone and in complex with the Herceptin Fab. Nature 421, 756-760 (2003).
50. Klosterman, P. S., Shah, S. A. & Steitz, T. A. Crystal structures of two plasmid copy control related RNA duplexes: an 18 base pair duplex at 1.20 Å resolution and a 19 base pair duplex at 1.55 Å resolution. Biochemistry 38, 14784-14792 (1999).
51. Mizuguchi, K., Parker, J. S., Blundell, T. L. & Gay, N. J. Getting knotted: a model for the structure and activation of Spätzle. Trends Biochem. Sci. 23, 239-242 (1998).