In Silico Analysis of nsSNPs of Carp TLR22 Gene Affecting its Binding Ability with Poly I:C

• Published in: Interdisciplinary sciences : computational life sciences Vol. 10; no. 4; pp. 641 - 652
• Main Authors: Chakrapani, Vemulawada, Rasal, Kiran D., Kumar, Sunil, Mohapatra, Shibani D., Sundaray, Jitendra K., Jayasankar, Pallipuram, Barman, Hirak K.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.12.2018; Springer Nature B.V
• Subjects: Affinity; Amphibians; Animals; Binding; Biomedical and Life Sciences; Carp; Carps - genetics; Computational Biology/Bioinformatics; Computational Science and Engineering; Computer Appl. in Life Sciences; Computer Simulation; Double-stranded RNA; Fish; Health Sciences; Immune response; Immune system; In vivo methods and tests; Leucine; Life Sciences; Ligands; Mathematical and Computational Physics; Medicine; Missense mutation; Molecular docking; Molecular Docking Simulation; Mutant Proteins - chemistry; Mutants; Mutation; Mutation, Missense - genetics; Original Research Article; Pathogens; Poly I-C - metabolism; Polyinosinic:polycytidylic acid; Polymorphism, Single Nucleotide - genetics; Protein Binding; Protein structure; Proteins; Ribonucleic acid; RNA; Signal transduction; Single-nucleotide polymorphism; Statistics for Life Sciences; Structural Homology, Protein; Structure-function relationships; Theoretical; Theoretical and Computational Chemistry; Three dimensional models; Toll-like receptors; Toll-Like Receptors - chemistry; Toll-Like Receptors - genetics; Transduction; TLR22 nsSNPs; Protein modelling; Docking simulation
• ISSN: 1913-2751; 1867-1462
• DOI: 10.1007/s12539-017-0247-2

Immune response mediated by toll-like receptor 22 (TLR22), only found in teleost/amphibians, is triggered by double-stranded RNA binding to its LRR (leucine-rich repeats) ecto-domain. Accumulated evidences suggested that missense mutations in TLR genes affect its function. However, information on mutation linked pathogen recognition for TLR22 was lacking. The present study was commenced for predicting the effect of non-synonymous single-nucleotide polymorphisms (nsSNPs) on the pathogen recognizable LRR domain of TLR22 of farmed carp, Labeo rohita. The sequence-based algorithms (SIFT, PROVEAN and I-Mutant2.0) indicated that three SNPs (out of 27) such as p.L159F (rs76759876) and p.L529P (rs749355507) of LRR, and p.I836M (rs750758397) of intracellular motifs could potentially disrupt protein function. The 3D structure was generated using MODELLER 9.13 and further validated by SAVEs server. The simulated molecular docking of native TLR22 and mutants with poly I:C ligand indicated that mutations positioned at p.L159F and p.L529P of the LRR region affects the binding affinity significantly. This is the first kind of study of predicting nsSNPs of teleost TLR22 with disturbed ligand binding affinity with its extra-cellular LRR domain and thereby likely hindrance in subsequent signal transduction. This study serves as a guide for in vivo evaluation of impact of mutation on immune response mediated by teleost TLR22 gene.