Toll-like Receptors

From Proteopedia

Glycosylated mouse toll-like receptor 3 dimer complex with double-stranded RNA 3ciy Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image Contents 1 Function 2 Relevance 3 3D Structures of Toll-like Receptors Function Toll-like receptors, often abbreviated TLRs, are found on the surface of phagocytic cells of vertebrates and invertebrates and are critical to the innate immune system. The Toll-like receptors recognize molecular patterns associated with pathogens, such as double-stranded RNA, lipopolysaccharide, or CpG DNA, and initiate an intracellular kinase cascade, inducing an immediate defensive response.[1][2] See Inflammation & Rheumatoid Arthritis. The receptors are multi-domain structures consisting of an extracellular ectodomain, a transmembrane domain and a intracellular Toll/IL-1 receptor domain. The extracellular domains contain leucine-rich repeats. See also Enzyme-linked receptor TLR signaling pathway TLR2 is likely involved in specific B cell-mediated functions[3]. TLR4 is the central lipid recognition protein in the lipopolysaccharide receptor complex[4]. TLR5 protects mice against Clostridium induced colitis [5]. TLR6 is involved in the discrimination of bacterial lipoproteins by the immune system[6]. TLR7 stimulation promotes autoimmune diabetes in mice[7]. TLR8 is linked to the control of CD4+ regulatory T cells[8]. TLR9 is involved in the activation of innate immunity[9]. TLR10 see Toll-like receptor 10. TLR13 is activated by a motif in bacterial ribosome 23S RNA and is not present in human[10].   Articles in Proteopedia concerning Toll-like Receptors include: Leucine-rich repeat Membrane proteins To view automatically seeded indices concerning Toll-like Receptors, see: Toll pathway Toll-like receptor Toll Toll like receptor adaptor domain TLR Relevance A variant of TLR3 confers protection agains geographical atrophy[11]. TLR3 is activated during viral infection[12]. TLR10 is a functional receptor involved in the innate immune response to H.pylori infection[13].     3D Structures of Toll-like Receptors Toll-like Receptor 3D structures

References and Notes

1. ↑ Gong J, Wei T, Zhang N, Jamitzky F, Heckl WM, Rossle SC, Stark RW. TollML: a database of toll-like receptor structural motifs. J Mol Model. 2010 Jul;16(7):1283-9. Epub 2010 Jan 19. PMID:20084417 doi:10.1007/s00894-009-0640-9
2. ↑ Arancibia SA, Beltran CJ, Aguirre IM, Silva P, Peralta AL, Malinarich F, Hermoso MA. Toll-like receptors are key participants in innate immune responses. Biol Res. 2007;40(2):97-112. Epub 2007 Nov 21. PMID:18064347 doi:/S0716-97602007000200001
3. ↑ Ganley-Leal LM, Liu X, Wetzler LM. Toll-like receptor 2-mediated human B cell differentiation. Clin Immunol. 2006 Sep;120(3):272-84. PMID:16766226 doi:http://dx.doi.org/10.1016/j.clim.2006.04.571
4. ↑ Lien E, Means TK, Heine H, Yoshimura A, Kusumoto S, Fukase K, Fenton MJ, Oikawa M, Qureshi N, Monks B, Finberg RW, Ingalls RR, Golenbock DT. Toll-like receptor 4 imparts ligand-specific recognition of bacterial lipopolysaccharide. J Clin Invest. 2000 Feb;105(4):497-504. PMID:10683379 doi:http://dx.doi.org/10.1172/JCI8541
5. ↑ Jarchum I, Liu M, Lipuma L, Pamer EG. Toll-like receptor 5 stimulation protects mice from acute Clostridium difficile colitis. Infect Immun. 2011 Apr;79(4):1498-503. doi: 10.1128/IAI.01196-10. Epub 2011 Jan, 18. PMID:21245274 doi:http://dx.doi.org/10.1128/IAI.01196-10
6. ↑ Takeuchi O, Kawai T, Muhlradt PF, Morr M, Radolf JD, Zychlinsky A, Takeda K, Akira S. Discrimination of bacterial lipoproteins by Toll-like receptor 6. Int Immunol. 2001 Jul;13(7):933-40. PMID:11431423
7. ↑ Lee AS, Ghoreishi M, Cheng WK, Chang TY, Zhang YQ, Dutz JP. Toll-like receptor 7 stimulation promotes autoimmune diabetes in the NOD mouse. Diabetologia. 2011 Jun;54(6):1407-16. doi: 10.1007/s00125-011-2083-y. Epub 2011, Feb 22. PMID:21340621 doi:http://dx.doi.org/10.1007/s00125-011-2083-y
8. ↑ Peng G, Guo Z, Kiniwa Y, Voo KS, Peng W, Fu T, Wang DY, Li Y, Wang HY, Wang RF. Toll-like receptor 8-mediated reversal of CD4+ regulatory T cell function. Science. 2005 Aug 26;309(5739):1380-4. PMID:16123302 doi:http://dx.doi.org/10.1126/science.1113401
9. ↑ Ashkar AA, Rosenthal KL. Toll-like receptor 9, CpG DNA and innate immunity. Curr Mol Med. 2002 Sep;2(6):545-56. PMID:12243247
10. ↑ Signorino G, Mohammadi N, Patane F, Buscetta M, Venza M, Venza I, Mancuso G, Midiri A, Alexopoulou L, Teti G, Biondo C, Beninati C. Role of Toll-like receptor 13 in innate immune recognition of group B streptococci. Infect Immun. 2014 Dec;82(12):5013-22. doi: 10.1128/IAI.02282-14. Epub 2014 Sep, 15. PMID:25225249 doi:http://dx.doi.org/10.1128/IAI.02282-14
11. ↑ . PMID:218753640
12. ↑ Stridh L, Mottahedin A, Johansson ME, Valdez RC, Northington F, Wang X, Mallard C. Toll-like receptor-3 activation increases the vulnerability of the neonatal brain to hypoxia-ischemia. J Neurosci. 2013 Jul 17;33(29):12041-51. doi: 10.1523/JNEUROSCI.0673-13.2013. PMID:23864690 doi:http://dx.doi.org/10.1523/JNEUROSCI.0673-13.2013
13. ↑ Nagashima H, Iwatani S, Cruz M, Jimenez Abreu JA, Uchida T, Mahachai V, Vilaichone RK, Graham DY, Yamaoka Y. Toll-like Receptor 10 in Helicobacter pylori Infection. J Infect Dis. 2015 Nov 15;212(10):1666-76. doi: 10.1093/infdis/jiv270. Epub 2015 , May 14. PMID:25977263 doi:http://dx.doi.org/10.1093/infdis/jiv270

See Also

• Antibody
• Leucine-Rich Repeat Proteins

Additional Literature

• Liu L, Botos I, Wang Y, Leonard JN, Shiloach J, Segal DM, Davies DR. Structural basis of toll-like receptor 3 signaling with double-stranded RNA. Science. 2008 Apr 18;320(5874):379-81. PMID:18420935 doi:320/5874/379
• Bell JK, Askins J, Hall PR, Davies DR, Segal DM. The dsRNA binding site of human Toll-like receptor 3. Proc Natl Acad Sci U S A. 2006 Jun 6;103(23):8792-7. Epub 2006 May 23. PMID:16720699 doi:10.1073/pnas.0603245103
• Nyman T, Stenmark P, Flodin S, Johansson I, Hammarstrom M, Nordlund P. The crystal structure of the human toll-like receptor 10 cytoplasmic domain reveals a putative signaling dimer. J Biol Chem. 2008 May 2;283(18):11861-5. Epub 2008 Mar 10. PMID:18332149 doi:10.1074/jbc.C800001200
• Chan SL, Low LY, Hsu S, Li S, Liu T, Santelli E, Le Negrate G, Reed JC, Woods VL Jr, Pascual J. Molecular mimicry in innate immunity: crystal structure of a bacterial TIR domain. J Biol Chem. 2009 Aug 7;284(32):21386-92. Epub 2009 Jun 17. PMID:19535337 doi:10.1074/jbc.C109.007591
• Botos I, Liu L, Wang Y, Segal DM, Davies DR. The toll-like receptor 3:dsRNA signaling complex. Biochim Biophys Acta. 2009 Sep-Oct;1789(9-10):667-74. Epub 2009 Jul 9. PMID:19595807 doi:10.1016/j.bbagrm.2009.06.005
• Istomin AY, Godzik A. Understanding diversity of human innate immunity receptors: analysis of surface features of leucine-rich repeat domains in NLRs and TLRs. BMC Immunol. 2009 Sep 3;10:48. PMID:19728889 doi:10.1186/1471-2172-10-48
• Satake H, Sasaki N. Comparative overview of toll-like receptors in lower animals. Zoolog Sci. 2010 Feb;27(2):154-61. PMID:20141420 doi:10.2108/zsj.27.154
• Matsushima N, Tanaka T, Enkhbayar P, Mikami T, Taga M, Yamada K, Kuroki Y. Comparative sequence analysis of leucine-rich repeats (LRRs) within vertebrate toll-like receptors. BMC Genomics. 2007 May 21;8:124. PMID:17517123 doi:10.1186/1471-2164-8-124
• Carpenter S, O'Neill LA. Recent insights into the structure of Toll-like receptors and post-translational modifications of their associated signalling proteins. Biochem J. 2009 Jul 29;422(1):1-10. PMID:19627256 doi:10.1042/BJ20090616
• Choe J, Kelker MS, Wilson IA. Crystal structure of human toll-like receptor 3 (TLR3) ectodomain. Science. 2005 Jul 22;309(5734):581-5. Epub 2005 Jun 16. PMID:15961631
• Gong J, Wei T, Zhang N, Jamitzky F, Heckl WM, Rossle SC, Stark RW. TollML: a database of toll-like receptor structural motifs. J Mol Model. 2010 Jul;16(7):1283-9. Epub 2010 Jan 19. PMID:20084417 doi:10.1007/s00894-009-0640-9
• Jin MS, Lee JO. Structures of the toll-like receptor family and its ligand complexes. Immunity. 2008 Aug 15;29(2):182-91. PMID:18701082 doi:10.1016/j.immuni.2008.07.007

External Resources

• TOLLML Database: database of toll-like receptor structural motifs
• Toll-like Receptors: November 2011 Molecule of the Month as part of the series of tutorials that are at the RCSB Protein Data Bank and written by David Goodsell