title: Elucidation of novel structural scaffold in rohu TLR2 and its binding site analysis with peptidoglycan, lipoteichoic acid and zymosan ligands, and downstream MyD88 adaptor protein.
abstract: Toll-like receptors (TLRs) play key roles in sensing wide array of microbial signatures and induction of innate immunity. TLR2 in fish resembles higher eukaryotes by sensing peptidoglycan (PGN) and lipoteichoic acid (LTA) of bacterial cell wall and zymosan of yeasts. However, in fish TLR2, no study yet describes the ligand binding motifs in the leucine rich repeat regions (LRRs) of the extracellular domain (ECD) and important amino acids in TLR2-TIR (toll/interleukin-1 receptor) domain that could be engaged in transmitting downstream signaling. We predicted these in a commercially important freshwater fish species rohu (Labeo rohita) by constructing 3D models of TLR2-ECD, TLR2-TIR, and MyD88-TIR by comparative modeling followed by 40 ns (nanosecond) molecular dynamics simulation (MDS) for TLR2-ECD and 20 ns MDS for TLR2-TIR and MyD88-TIR. Protein (TLR2-ECD)-ligands (PGN, LTA, and zymosan) docking in rohu by AutoDock4.0, FlexX2.1, and GOLD4.1 anticipated LRR16-19, LRR12-14, and LRR20-CT as the most important ligand binding motifs. Protein (TLR2-TIR)-protein (MyD88-TIR) interaction by HADDOCK and ZDOCK predicted BB loop, α B-helix, α C-helix, and CD loop in TLR2-TIR and BB loop, α B-helix, and CD loop in MyD88-TIR as the critical binding domains. This study provides ligands recognition and downstream signaling.
authors: Fish Health Management Division, Central Institute of Freshwater Aquaculture (CIFA), Kausalyaganga, Bhubaneswar, Odisha 751002, India.
authors: Bikash Ranjan
authors: BR
authors: Sahoo
authors: Madhubanti
authors: M
authors: Basu
authors: Banikalyan
authors: B
authors: Swain
authors: Manas Ranjan
authors: MR
authors: Dikhit
authors: Pallipuram
authors: P
authors: Jayasankar
authors: Mrinal
authors: M
authors: Samanta
mesh_terms: D000818:Animals; D001665:Binding Sites; D003530:Cyprinidae; D007113:Immunity, Innate / Q000235:genetics; D050856:Interferon Regulatory Factor-1 / Q000737:chemistry; D008024:Ligands; D008070:Lipopolysaccharides / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D010457:Peptidoglycan / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D013682:Teichoic Acids / Q000737:chemistry*; D051195:Toll-Like Receptor 2 / Q000737:chemistry*; D015054:Zymosan / Q000737:chemistry*
chemical_list: D050856:Interferon Regulatory Factor-1; D008024:Ligands; D008070:Lipopolysaccharides; D010457:Peptidoglycan; D013682:Teichoic Acids; D051195:Toll-Like Receptor 2; C009900:lipoteichoic acid; D015054:Zymosan
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