Skip to main content
SpringerLink
Log in

TollML: a database of toll-like receptor structural motifs

  • Original Paper
  • Published:
Journal of Molecular Modeling Aims and scope Submit manuscript

Abstract

Toll-like receptors (TLRs) play a key role in the innate immune system. TLRs recognize pathogen-associated molecular patterns and initiate an intracellular kinase cascade to induce an immediate defensive response. During recent years TLRs have become the focus of tremendous research interest. A central repository for the growing amount of relevant TLR sequence information has been created. Nevertheless, structural motifs of most sequenced TLR proteins, such as leucine-rich repeats (LRRs), are poorly annotated in the established databases. A database that organizes the structural motifs of TLRs could be useful for developing pattern recognition programs, structural modeling and understanding functional mechanisms of TLRs. We describe TollML, a database that integrates all of the TLR sequencing data from the NCBI protein database. Entries were first divided into TLR families (TLR1-23) and then semi-automatically subdivided into three levels of structural motif categories: (1) signal peptide (SP), ectodomain (ECD), transmembrane domain (TD) and Toll/IL-1 receptor (TIR) domain of each TLR; (2) LRRs of each ECD; (3) highly conserved segment (HCS), variable segment (VS) and insertions of each LRR. These categories can be searched quickly using an easy-to-use web interface and dynamically displayed by graphics. Additionally, all entries have hyperlinks to various sources including NCBI, Swiss-Prot, PDB, LRRML and PubMed in order to provide broad external information for users. The TollML database is available at http://tollml.lrz.de.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Anderson KV, Bokla L, Nusslein-Volhard C (1985) Establishment of dorsal-ventral polarity in the Drosophila embryo: the induction of polarity by the Toll gene product. Cell 42:791–798

    Article  CAS  Google Scholar 

  2. Takeda K, Akira S (2005) Toll-like receptors in innate immunity. Int Immunol 17:1–14

    Article  CAS  Google Scholar 

  3. Brodsky I, Medzhitov R (2007) Two modes of ligand recognition by TLRs. Cell 130:979–981

    Article  CAS  Google Scholar 

  4. Gay NJ, Gangloff M (2007) Structure and function of Toll receptors and their ligands. Annu Rev Biochem 76:141–165

    Article  CAS  Google Scholar 

  5. Barton GM, Kagan JC, Medzhitov R (2006) Intracellular localization of Toll-like receptor 9 prevents recognition of self DNA but facilitates access to viral DNA. Nat Immunol 7:49–56

    Article  CAS  Google Scholar 

  6. O'Neill LA, Bowie AG (2007) The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling. Nat Rev Immunol 7:353–364

    Article  Google Scholar 

  7. Kobe B, Kajava AV (2001) The leucine-rich repeat as a protein recognition motif. Curr Opin Struct Biol 11:725–732

    Article  CAS  Google Scholar 

  8. Wei T, Gong J, Jamitzky F, Heckl WM, Stark RW, Roessle SC (2008) LRRML: a conformational database and an XML description of leucine-rich repeats (LRRs). BMC Struct Biol 8:47

    Article  Google Scholar 

  9. Matsushima N, Tanaka T, Enkhbayar P, Mikami T, Taga M, Yamada K, Kuroki Y (2007) Comparative sequence analysis of leucine-rich repeats (LRRs) within vertebrate toll-like receptors. BMC Genomics 8:124

    Article  Google Scholar 

  10. Xu Y, Tao X, Shen B, Horng T, Medzhitov R, Manley JL, Tong L (2000) Structural basis for signal transduction by the Toll/interleukin-1 receptor domains. Nature 408:111–115

    Article  CAS  Google Scholar 

  11. Bell JK, Botos I, Hall PR, Askins J, Shiloach J, Segal DM, Davies DR (2005) The molecular structure of the Toll-like receptor 3 ligand-binding domain. Proc Natl Acad Sci USA 102:10976–10980

    Article  CAS  Google Scholar 

  12. Choe J, Kelker MS, Wilson IA (2005) Crystal structure of human toll-like receptor 3 (TLR3) ectodomain. Science 309:581–585

    Article  CAS  Google Scholar 

  13. Jin MS, Kim SE, Heo JY, Lee ME, Kim HM, Paik SG, Lee H, Lee JO (2007) Crystal structure of the TLR1-TLR2 heterodimer induced by binding of a tri-acylated lipopeptide. Cell 130:1071–1082

    Article  CAS  Google Scholar 

  14. Kim HM, Park BS, Kim JI, Kim SE, Lee J, Oh SC, Enkhbayar P, Matsushima N, Lee H, Yoo OJ, Lee JO (2007) Crystal structure of the TLR4-MD-2 complex with bound endotoxin antagonist Eritoran. Cell 130:906–917

    Article  CAS  Google Scholar 

  15. Liu L, Botos I, Wang Y, Leonard JN, Shiloach J, Segal DM, Davies DR (2008) Structural basis of toll-like receptor 3 signaling with double-stranded RNA. Science 320:379–381

    Article  CAS  Google Scholar 

  16. Park BS, Song DH, Kim HM, Choi BS, Lee H, Lee JO (2009) The structural basis of lipopolysaccharide recognition by the TLR4-MD-2 complex. Nature 458:1191–1195

    Article  CAS  Google Scholar 

  17. Dolan J, Walshe K, Alsbury S, Hokamp K, O'Keeffe S, Okafuji T, Miller SF, Tear G, Mitchell KJ (2007) The extracellular leucine-rich repeat superfamily; a comparative survey and analysis of evolutionary relationships and expression patterns. BMC Genomics 8:320

    Article  Google Scholar 

  18. Wheeler DL, Barrett T, Benson DA, Bryant SH, Canese K, Chetvernin V, Church DM, Dicuccio M, Edgar R, Federhen S, Feolo M, Geer LY, Helmberg W, Kapustin Y, Khovayko O, Landsman D, Lipman DJ, Madden TL, Maglott DR, Miller V, Ostell J, Pruitt KD, Schuler GD, Shumway M, Sequeira E, Sherry ST, Sirotkin K, Souvorov A, Starchenko G, Tatusov RL, Tatusova TA, Wagner L, Yaschenko E (2008) Database resources of the National Center for Biotechnology Information. Nucleic Acids Res 36:D13–D21

    Article  CAS  Google Scholar 

  19. Rost B, Yachdav G, Liu J (2004) The PredictProtein server. Nucleic Acids Res 32:W321–W326

    Article  CAS  Google Scholar 

  20. Kneller DG, Cohen FE, Langridge R (1990) Improvements in protein secondary structure prediction by an enhanced neural network. J Mol Biol 214:171–182

    Article  CAS  Google Scholar 

  21. Bryson K, McGuffin LJ, Marsden RL, Ward JJ, Sodhi JS, Jones DT (2005) Protein structure prediction servers at University College London. Nucleic Acids Res 33:W36–W38

    Article  CAS  Google Scholar 

  22. Pollastri G, Przybylski D, Rost B, Baldi P (2002) Improving the prediction of protein secondary structure in three and eight classes using recurrent neural networks and profiles. Proteins 47:228–235

    Article  CAS  Google Scholar 

  23. Wu CH, Apweiler R, Bairoch A, Natale DA, Barker WC, Boeckmann B, Ferro S, Gasteiger E, Huang H, Lopez R, Magrane M, Martin MJ, Mazumder R, O'Donovan C, Redaschi N, Suzek B (2006) The Universal Protein Resource (UniProt): an expanding universe of protein information. Nucleic Acids Res 34:D187–D191

    Article  CAS  Google Scholar 

  24. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE (2000) The Protein Data Bank. Nucleic Acids Res 28:235–242

    Article  CAS  Google Scholar 

  25. PubMed: http://www.ncbi.nlm.nih.gov/pubmed

  26. Finn RD, Tate J, Mistry J, Coggill PC, Sammut SJ, Hotz HR, Ceric G, Forslund K, Eddy SR, Sonnhammer EL, Bateman A (2008) The Pfam protein families database. Nucleic Acids Res 36:D281–D288

    Article  CAS  Google Scholar 

  27. Mulder N, Apweiler R (2007) InterPro and InterProScan: tools for protein sequence classification and comparison. Methods Mol Biol 396:59–70

    Article  CAS  Google Scholar 

  28. Schultz J, Copley RR, Doerks T, Ponting CP, Bork P (2000) SMART: a web-based tool for the study of genetically mobile domains. Nucleic Acids Res 28:231–234

    Article  CAS  Google Scholar 

  29. eXist: http://exist-db.org

  30. The World Wide Web Consortium: http://www.w3.org

  31. Notredame C, Higgins DG, Heringa J (2000) T-Coffee: A novel method for fast and accurate multiple sequence alignment. J Mol Biol 302:205–217

    Article  CAS  Google Scholar 

  32. WU-BLAST: http://blast.wustl.edu

  33. Wei T, Gong J, Jamitzky F, Heckl WM, Stark RW, Rossle SC (2009) Homology modeling of human Toll-like receptors TLR7, 8, and 9 ligand-binding domains. Protein Sci 18:1684–1691

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by Graduiertenkolleg 1202 of the Deutsche Forschungsgemeinschaft (DFG) and the DFG excellence cluster Nanosystems Initiative Munich (NIM).

Author information

Authors and Affiliations

  1. Center for Nanoscience, Ludwig-Maximilians-Universität München, 80799, Munich, Germany

    Jing Gong, Tiandi Wei, Ferdinand Jamitzky, Wolfgang M. Heckl & Robert W. Stark

  2. Department of Earth and Environmental Sciences, Ludwig-Maximilians-Universität München, Theresienstr. 41, 80333, Munich, Germany

    Jing Gong, Tiandi Wei, Shaila C. Rössle & Robert W. Stark

  3. Department of Informatics, Ludwig-Maximilians-Universität München, 80333, Munich, Germany

    Ning Zhang

  4. Leibniz Supercomputing Centre, 85748, Garching, Germany

    Ferdinand Jamitzky

  5. Deutsches Museum, 80538, Munich, Germany

    Wolfgang M. Heckl

  6. TUM School of Education, Technische Universität München, 80799, Munich, Germany

    Wolfgang M. Heckl

Authors
  1. Jing Gong
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tiandi Wei
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ning Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ferdinand Jamitzky
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Wolfgang M. Heckl
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shaila C. Rössle
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Robert W. Stark
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tiandi Wei.

Electronic supplementary materials

Below is the link to the electronic supplementary material.

Supplementary File 1

Document type definition (DTD) file of TollML (PDF 33 kb)

Supplementary File 2

XML Stylesheet (XSLT) of a TollML entry (PDF 51 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gong, J., Wei, T., Zhang, N. et al. TollML: a database of toll-like receptor structural motifs. J Mol Model 16, 1283–1289 (2010). https://doi.org/10.1007/s00894-009-0640-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00894-009-0640-9

Keywords

Search

Navigation