Advertisement

Journal of Biosciences

, 44:18 | Cite as

Insights into the evolution of extracellular leucine-rich repeats in metazoans with special reference to Toll-like receptor 4

  • Dipanjana Dhar
  • Debayan Dey
  • Soumalee BasuEmail author
Article
  • 101 Downloads

Abstract

The importance of the widely spread leucine-rich repeat (LRR) motif was studied considering TLRs, the LRR-containing protein involved in animal immune response. The protein connects intracellular signalling with a chain of molecular interactions through the presence of LRRs in the ectodomain and TIR in the endodomain. Domain analyses with human TLR1-9 reported ectodomain with tandem repeats, transmembrane domain and TIR domain. The repeat number varied across members of TLR and remained characteristic to a particular member. Analysis of gene structure revealed absence of codon interruption with TLR3 and TLR4 as exceptions. Extensive study with TLR4 from metazoans confirmed the presence of 23 LRRs in tandem. Distinct clade formation using coding and amino acid sequence of individual repeats illustrated independent evolution. Although ectodomain and endodomain exhibited differential selection pressure, within the ectodomain, however, the individual repeats displayed positive, negative and neutral selection pressure depending on their structural and functional significance.

Keywords

Codon interruption domain architecture evolution gene structure intron phase leucine-rich repeat phylogenetics selection pressure tandem arrays Toll-like receptors 

Notes

Acknowledgements

The authors gratefully acknowledge the facilities provided by the Centre for High-Performance Computing for Modern Biology (CHPC) in the University of Calcutta. The authors express their sincere gratitude to Dr Aditi Maulik, postdoctoral (Wellcome Trust) fellow at the Indian Institute of Science, and Ms Sucharita Das, senior research fellow at the University of Calcutta, who provided insight and expertise that greatly assisted this research work.

Supplementary material

12038_2018_9821_MOESM1_ESM.pdf (1.8 mb)
Supplementary material 1 (PDF 1891 kb)

References

  1. Aken BL, Achuthan P, Akanni W, Amode MR, Bernsdorff F, Bhai J, Billis K, Carvalho-Silva D, et al. 2017 Ensembl 2017. Nucleic Acids Res. 45 635–642CrossRefGoogle Scholar
  2. Akira S 2003 Toll-like receptor signalling. J. Biol. Chem. 278 38105–38108CrossRefGoogle Scholar
  3. Akira S and Takeda K 2004 Toll-like receptor signalling. Nat. Rev. Immunol. 4 499–511CrossRefGoogle Scholar
  4. Altschul SF, Gish W, Miller W, Myers EW and Lipman DJ 1990 Basic local alignment search tool. J. Mol. Biol. 215 403–410CrossRefGoogle Scholar
  5. Bella J, Hindle KL, McEwan PA and Lovell SC 2008 The leucine-rich repeat structure. Cell. and Mol. Life Sci. 65 2307–2333CrossRefGoogle Scholar
  6. Botos I, Segal DM and Davies DR 2011 The structural biology of Toll-Like receptors. Structure 19 447–459CrossRefGoogle Scholar
  7. Burge S, Kelly E, Lonsdale D, Mutowo-Muellenet P, McAnulla C, Mitchell A, Sangrador-Vegas A, Yong S, Mulder N and Hunter S 2012 Manual GO annotation of predictive protein signatures: the InterPro approach to GO curation. Database Article ID bar068Google Scholar
  8. Butcher SK, O’Carroll CE, Wells CA and Carmody RJ 2018 Toll-Like receptors drive specific patterns of tolerance and training on restimulation of macrophages. Front. Immunol. 9 933CrossRefGoogle Scholar
  9. de Wit J, Hong W, Luo L and Ghosh A 2011 Role of leucine-rich repeat proteins in the development and function of neural circuits. Annu. Rev. Cell Dev. Biol. 27 697–729CrossRefGoogle Scholar
  10. Felsenstein J 1989 PHYLIP: Phylogeny inference package. Cladistics 5 164–166Google Scholar
  11. Hasan U, Chaffois C, Gaillard C, Saulnier V, Merck E, Tancredi S, Guiet C, Brière F, Vlach J, Lebecque S, Trinchieri G, and Bates EEM 2005 Human TLR10 is a functional receptor, expressed by B cells and plasmacytoid dendritic cells, which activates gene transcription through MyD88. J. Immunol. 174 2942–2950CrossRefGoogle Scholar
  12. Huang S, Yuan S, Guo L, Yu Y, Li J, Wu T, Liu T, Yang M, Wu K, Liu H, Ge J, Yu Y, Huang H, Dong M, Yu C, Chen S, and Xu A 2008 Genomic analysis of the immune gene repertoire of amphioxus reveals extraordinary innate complexity and diversity. Genome Res. 18 1112–1126CrossRefGoogle Scholar
  13. Hughes AL and Piontkivska H 2008 Functional diversification of the toll-like receptor gene family. Immunogenetics 60 249–256CrossRefGoogle Scholar
  14. Kajava AV, Vassart G and Wodak SJ 1995 Modeling of the three-dimensional structure of proteins with the typical leucine-rich repeats. Structure 3 867–877CrossRefGoogle Scholar
  15. Kajava AV 1998 Stuctural diversity of leucine-rich repeat proteins. J. Mol. Biol. 277 519–527CrossRefGoogle Scholar
  16. Kobe B and Deisenhofer J 1994 The leucine-rich repeat: a versatile binding motif. Trends Biochem. Sci. 19 415–421CrossRefGoogle Scholar
  17. Kobe B and Kajava AV 2001 The leucine-rich repeat as a protein recognition motif. Curr. Opin. Struct. Biol. 11 725–732CrossRefGoogle Scholar
  18. Krieg AM and Vollmer J 2007 Toll-like receptors 7, 8, and 9: linking innate immunity to autoimmunity. Immunol. Rev. 220 251–269CrossRefGoogle Scholar
  19. Letunic I, Doerks T and Bork P 2012 SMART 7: recent updates to the protein domain annotation resource. Nucleic Acids Res. 40 302–305CrossRefGoogle Scholar
  20. Letunic I and Bork P 2016 Interactive tree of life (iTOL) v3: an online tool for the display and annotation of phylogenetic and other trees. Nucleic Acids Res. 44 242–245CrossRefGoogle Scholar
  21. Liberles DA 2001 Evaluation of methods for determination of a reconstructed history of gene sequence evolution. Mol. Biol. Evol. 18 2040–2047CrossRefGoogle Scholar
  22. Matsushima N, Enkhbayar P, Kamiya M, Osaki M and Kretsinger RH 2005a Leucine-Rich repeats (LRRs): Structure, function, evolution and interaction with ligands. Drug Des. Rev. 2 305–322CrossRefGoogle Scholar
  23. Matsushima N, Tachi N, Kuroki Y, Enkhbayar P, Osaki M, Kamiya M and Kretsinger RH 2005b Structural analysis of leucine-rich-repeat variants in proteins associated with human diseases. Cell. Mol. Life Sci. 62 2771–2791CrossRefGoogle Scholar
  24. Matsushima N, Tanaka T, Enkhbayar P, Mikami T, Taga M, Yamada K and Kuroki Y 2007 Comparative sequence analysis of leucine-rich repeats (LRRs) within vertebrate toll-like receptors. BMC Genomics 8 124CrossRefGoogle Scholar
  25. Matsushima N, Miyashita H, Mikami T and Kuroki Y 2010 A nested leucine rich repeat (LRR) domain: the precursor of LRRs is a ten or eleven residue motif. BMC Microbiol. 10 235CrossRefGoogle Scholar
  26. Medzhitov R 2007 Recognition of microorganisms and activation of the immune response. Nature 449 819–826CrossRefGoogle Scholar
  27. Mikami T, Miyashita H, Takatsuka S, Kuroki Y and Matsushima N 2012 Molecular evolution of vertebrate Toll-like receptors: evolutionary rate difference between their leucine-rich repeats and their TIR domains. Gene 503 235–243CrossRefGoogle Scholar
  28. Notredame C, Higgins DG and Heringa J 2000 T-Coffee: a novel method for fast and accurate multiple sequence alignment. J. Mol. Biol. 302 205–217CrossRefGoogle Scholar
  29. Ng A and Xavier RJ 2011 Leucine-rich repeat (LRR) proteins: integrators of pattern recognition and signalling in immunity. Autophagy 7 1082–1084CrossRefGoogle Scholar
  30. Ohyanagi T and Matsushima N 1997 Classification of tandem leucine-rich repeats within a great variety of proteins. 11 949Google Scholar
  31. O’Neill JA and Bowie AG 2007 The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling. Nat. Rev. Immunol. 7 353–364CrossRefGoogle Scholar
  32. Park BS, Song DH, Kim HM, Choi BS, Lee H and Lee JO 2009 The structural basis of lipopolysaccharide recognition by the TLR4–MD-2 complex. Nature 458 1191–1195CrossRefGoogle Scholar
  33. Piatigorsky J 2007 Gene sharing an evolution: the diversity of protein functions (Harvard University Press, Cambridge MA)CrossRefGoogle Scholar
  34. Poirot O, O’Toole E and Notredame C 2003 Tcoffee@igs: a web server for computing, evaluating and combining multiple sequence alignments. Nucleic Acids Res. 31 3503–3506CrossRefGoogle Scholar
  35. Roach JC, Glusman G, Rowen L, Kaur A, Purcell MK, Smith KD, Hood LE and Aderem A 2005 The evolution of vertebrate Toll-like receptors. PNAS 102 9577–9582CrossRefGoogle Scholar
  36. Roach JM, Racioppi L, Jones CD and Masci AM 2013 Phylogeny of Toll-like receptor signalling: adapting the innate response. PLOS ONE 8 Google Scholar
  37. Sharp PA 1981 Speculations on RNA splicing. Cell 23 643–646CrossRefGoogle Scholar
  38. Sigrist CJ, Cerutti L, de Castro E, Langendijk-Genevaux PS, Bulliard V, Bairoch A and Hulo N 2010 PROSITE, a protein domain database for functional characterization and annotation. Nucleic Acids Res. 38 161–166CrossRefGoogle Scholar
  39. Sonnhammer ELL, Eddy SR and Durbin R 1997 Pfam: a comprehensive database of protein domain families based on seed alignments. Proteins 28 405–420CrossRefGoogle Scholar
  40. Suyama M, Torrents D and Bork P 2006 PAL2NAL: robust conversion of protein sequence alignments into the corresponding codon alignments. Nucleic Acids Res. 34 609–612CrossRefGoogle Scholar
  41. Takeda K, Kaisho T and Akira S 2003 Toll-like receptors. Annu. Rev. Immunol. 21 335–376CrossRefGoogle Scholar
  42. The UniProt Consortium 2017 UniProt: the universal protein knowledgebase. Nucleic Acids Res. 45 158–169CrossRefGoogle Scholar
  43. Thompson JD, Higgins DG and Gibson TJ 1994 CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res. 22 4673–4680CrossRefGoogle Scholar
  44. Vidya MK, Kumar VG, Sejian V, Bagath M, Krishnan G and Bhatta R 2018 Toll-like receptors: significance, ligands, signaling pathways, and functions in mammals. Int. Rev. Immunol. 37 20–36CrossRefGoogle Scholar
  45. Wlasiuk G and Nachman MW 2010 Adaptation and constraint at Toll-like receptors in primates. Mol. Biol. Evol. 27 2172–2186CrossRefGoogle Scholar
  46. West AP, Koblansky AA and Ghosh S 2006 Recognition and signalling by Toll-like receptors. Annu. Rev. Cell Develop. Biol. 22 409–437CrossRefGoogle Scholar
  47. Yu L and Feng Z 2018 The role of Toll-like receptor signaling in the progression of heart failure. Med. Inflamm. 2018 Article ID 9874109, 11Google Scholar

Copyright information

© Indian Academy of Sciences 2019

Authors and Affiliations

  1. 1.Department of MicrobiologyUniversity of CalcuttaKolkataIndia

Personalised recommendations