Activation of Nucleotide-Binding Oligomerization Domain 1 (NOD1) Receptor Signaling in Labeo rohita by iE-DAP and Identification of Ligand-Binding Key Motifs in NOD1 by Molecular Modeling and Docking |
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Authors: | Bikash Ranjan Sahoo Banikalyan Swain Manas Ranjan Dikhit Madhubanti Basu Aritra Bej Pallipuram Jayasankar Mrinal Samanta |
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Affiliation: | 1. Fish Health Management Division, Central Institute of Freshwater Aquaculture (CIFA), Kausalyaganga, Bhubaneswar, Odisha, India, 751002 2. Biomedical Informatics Centre, Rajendra Memorial Research Institute of Medical Sciences, Agamkuan, Patna, Bihar, India, 800007 3. Central Institute of Freshwater Aquaculture (CIFA), Kausalyaganga, Bhubaneswar, Odisha, India, 751002
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Abstract: | The nucleotide-binding oligomerization domain 1 (NOD1) receptor recognizes various pattern-associated structures of microbes through its leucine-rich repeat (LRR) domain and activates signaling cascades to induce innate immunity. This report describes the activation of NOD1 receptor signaling by gamma-d-glutamyl-meso-diaminopimelic acid (or γ-D-Glu-mDAP [iE-DAP]) in a commercially important fish species, rohu (Labeo rohita). It also described critical motifs in the NOD1-LRR domain that could be involved in binding iE-DAP, lipopolysaccharide (LPS), and polyinosinic:polycytidylic acid (poly I:C). The activation of NOD1 receptor signaling was studied by injecting iE-DAP, and analysis of tissue samples for NOD1 and receptor-interacting serine/threonine kinase (RICK) expression was done by quantitative real-time polymerase chain reaction (qRT-PCR) assay. To identify ligand-binding motifs in NOD1, the 3D model of NOD1-LRR was generated, followed by a 6-ns molecular dynamics simulation. Molecular docking of LPS with NOD1-LRR was executed at the Hex and PatchDock servers, and iE-DAP and poly I:C in the AutoDock 4.2, FlexX 2.1, Glide 5.5, and GOLD 4.1 programs. The results of qRT-PCR revealed significant (p?0.05) upregulation of NOD1 and RICK expression. Molecular docking revealed that the amino acid residues at LRR1–2, LRR3–7, and LRR8–9 could be involved in poly I:C, LPS, and iE-DAP binding, respectively. In fish, this is the first report describing the 3D structure of NOD1-LRR and its critical ligand-binding motifs. |
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