Toll-like Receptors: Difference between revisions

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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.<ref>PMID: 20084417</ref><ref>PMID: 18064347</ref> 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]].
<StructureSection load='' size='340' side='right' caption='Glycosylated mouse toll-like receptor 3 dimer complex with double-stranded RNA [[3ciy]]' scene='Toll-like_Receptors/3ciynice/1' >
__TOC__
== 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.<ref>PMID: 20084417</ref><ref>PMID: 18064347</ref> 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<ref>PMID:16766226</ref>.<br />
 
*'''TLR4''' is the central lipid recognition protein in the lipopolysaccharide receptor complex<ref>PMID:10683379</ref>.<br />
[[Image:3ciyPV3D.png|left|thumb|360px|<span style="font-size:1.2em;">Extracellular domain of mouse Toll-like receptor dimer bound to double-stranded RNA which is a molecular signature of many viruses, from [[3ciy]].</span>]]
*'''TLR5''' protects mice against ''Clostridium'' induced colitis <ref>PMID:21245274</ref>.<br />
*'''TLR6''' is involved in the discrimination of bacterial lipoproteins by the immune system<ref>PMID:11431423</ref>.<br />
*'''TLR7''' stimulation promotes autoimmune diabetes in mice<ref>PMID:21340621</ref>.<br />
*'''TLR8''' is linked to the control of CD4+ regulatory T cells<ref>PMID:16123302</ref>.<br />
*'''TLR9''' is involved in the activation of innate immunity<ref>PMID:12243247</ref>.<br />
*'''TLR10''' see [[:Category:Toll-like receptor 10|Toll-like receptor 10]].<br />
*'''TLR13''' is activated by a motif in bacterial ribosome 23S RNA and is not present in human<ref>PMID:25225249</ref>.<br />


<br>&nbsp;<br>
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Articles in Proteopedia concerning Toll-like Receptors include:
Articles in Proteopedia concerning Toll-like Receptors include:
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*[[:Category:Toll pathway|Toll pathway]]
*[[:Category:Toll pathway|Toll pathway]]
*[[:Category:Toll-like receptor|Toll-like receptor]]
*[[:Category:Toll-like receptor|Toll-like receptor]]
*[[:Category:Toll-like receptor 10|Toll-like receptor 10]]
*[[:Category:Toll|Toll]]
*[[:Category:Toll|Toll]]
*[[:Category:Toll like receptor adaptor domain|Toll like receptor adaptor domain]]
*[[:Category:Toll like receptor adaptor domain|Toll like receptor adaptor domain]]
*[[:Category:Tlr|TLR]]
*[[:Category:Tlr|TLR]]
   
 
== Relevance ==
A variant of TLR3 confers protection agains geographical atrophy<ref>PMID:218753640</ref>. TLR3 is activated during viral infection<ref>PMID:23864690</ref>. TLR10 is a functional receptor involved in the innate immune response to ''H.pylori'' infection<ref>PMID:25977263</ref>.
   
   
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{{STRUCTURE_3ciy|  PDB=3ciy  | SIZE=400| SCENE=Toll-like_Receptors/3ciynice/1 |right|CAPTION=Mouse toll-like receptor 3 dimer complex with double-stranded RNA [[3ciy]] }}
==3D Structures of Toll-like Receptors==
==3D Structures of Toll-like Receptors==
[[Toll-like Receptor 3D structures]]


''Updated December 2011''
</StructureSection>
 
===TLR1===
 
[[1fyv]] – hTLR1 TIR domain – human<br />
[[2z7x]], [[2z81]], [[2z82]] – hTLR1/VLRB.61 + hTLR2/VLRB.61 + lipopeptide
 
===TLR2===
 
[[1fyw]] – hTLR2 TIR domain<br />
[[1fyx]], [[1o77]] - hTLR2 TIR domain (mutant) <br />
[[2z80]] – hTLR2/VLRB.61<br />
[[3a7b]] - mTLR2/VLRB.61 – mouse<br />
[[3a7c]] - mTLR2/VLRB.61 + PE-DTPA<br />
[[3a79]] – hTLR2/VLRB.61 + hTLR6/VLRB.61 + lipopeptide
 
===TLR3===
 
[[1ziw]], [[2a0z]] – hTLR3 ligand-binding domain<br />
[[3cig]] – mTLR3 ectodomain<br />
[[3ciy]] - mTLR3 ectodomain + RNA
 
===TLR4===
 
[[2z62]], [[2z63]], [[2z66]] – hTLR4/VLRB.61<br />
[[2z64]], [[2z65]] – mTLR4 extracellular domain+ lymphocyte antigen 96<br />
[[3fxi]] - hTLR4 extracellular domain + lymphocyte antigen 96
===TLR10===
 
[[2j67]] – hTLR10 TIR domain
 


==References and Notes==
==References and Notes==
<references/>
<references/>


==See Also==
==See Also==

Latest revision as of 14:11, 19 January 2023

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

  • 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:


To view automatically seeded indices concerning Toll-like Receptors, see:

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


Glycosylated mouse toll-like receptor 3 dimer complex with double-stranded RNA 3ciy

Drag the structure with the mouse to rotate

References and NotesReferences 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 AlsoSee Also

Additional LiteratureAdditional Literature

[xtra 1][xtra 2][xtra 3][xtra 4][xtra 5][xtra 6][xtra 7][xtra 8][xtra 9][xtra 10][xtra 11][xtra 12]

  1. ↑ 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
  2. ↑ 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
  3. ↑ 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
  4. ↑ 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
  5. ↑ 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
  6. ↑ 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
  7. ↑ 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
  8. ↑ 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
  9. ↑ 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
  10. ↑ 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
  11. ↑ 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
  12. ↑ 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

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