header logo image header logo text
Downloads Login
General Information
ZFIN ID: ZDB-PUB-141210-14
Understanding the distinguishable structural and functional features in zebrafish TLR3 and TLR22, and their binding modes with fish dsRNA viruses: an exploratory structural model analysis
Sahoo, B.R., Dikhit, M.R., Bhoi, G.K., Maharana, J., Lenka, S.K., Dubey, P.K., Tiwari, D.K.
Date: 2015
Source: Amino Acids   47(2): 381-400 (Journal)
Registered Authors:
Keywords: none
MeSH Terms:
  • Animals
  • Molecular Dynamics Simulation*
  • Protein Binding
  • RNA Viruses/chemistry*
  • RNA Viruses/metabolism
  • RNA, Double-Stranded/chemistry*
  • RNA, Double-Stranded/metabolism
  • RNA, Viral/chemistry*
  • RNA, Viral/metabolism
  • Repetitive Sequences, Amino Acid
  • Toll-Like Receptor 3/chemistry*
  • Toll-Like Receptor 3/genetics
  • Toll-Like Receptor 3/metabolism
  • Zebrafish*
  • Zebrafish Proteins/chemistry*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed: 25488424 Full text @ Amino Acids
Viral infections are one of the major challenges in aquaculture production, and considered as the potential threat for fish farming. Toll-like receptor (TLR) 3 and TLR22 are highly specialized innate immune receptors that recognize double-stranded (ds)-RNA of viruses resulting in the induction of innate immunity. The existence of TLR3 and TLR22 only in aquatic animals indicates their distinctive characteristics in viral infection; however, the studies in exploring their structural features and dsRNA binding mechanism are still elusive. Here, we studied the structural and functional differentiations of TLR3 and TLR22 in zebrafish by employing comparative modeling and molecular dynamics simulation. Comparative structural analysis revealed a distinct spatial arrangement of TLR22 ectodomain with a flattened horseshoe-shape conformation as compared to other TLRs. Essential dynamics studies showed that unlike TLR3, TLR22 possessed a prominent motion, elasticity and twisting at both terminus separated by a distance equivalent to the length of a short-sized dsRNA. Interaction analysis of polyinosinic:polycytidylic acid (poly I:C) and dsRNA depicted leucine-rich-repeats (LRR)2-3 and LRR18-19 (in TLR3) and LRRNT-LRR3 and LRR22-24 (in TLR22) as the potential binding sites. The short-sized dsRNA binds tightly across its full-length with TLR22-monomer, and suggested that TLR22 dimer may sense long-sized dsRNA. Binding energy (BE) calculation using MM/PBSA method from the TLR3- and TLR22-ligand complexes revealed an adequate binding affinity between TLR22-monomer and dsRNA as like as TLR3-dimer-dsRNA complex. Mutagenesis and BE computation of key residues suggested their involvement in dsRNA recognition. These findings can be helpful for therapeutic applications against viral diseases in fish.