title: 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.
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.
authors: Fish Health Management Division, Central Institute of Freshwater Aquaculture, Kausalyaganga, Bhubaneswar, Odisha, India 751002.
authors: Bikash Ranjan
authors: BR
authors: Sahoo
authors: Banikalyan
authors: B
authors: Swain
authors: Manas Ranjan
authors: MR
authors: Dikhit
authors: Madhubanti
authors: M
authors: Basu
authors: Aritra
authors: A
authors: Bej
authors: Pallipuram
authors: P
authors: Jayasankar
authors: Mrinal
authors: M
authors: Samanta
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D001665:Binding Sites; D003198:Computer Simulation; D003531:Cypriniformes / Q000378:metabolism*; D003960:Diaminopimelic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D008024:Ligands; D008954:Models, Biological; D008956:Models, Chemical; D008958:Models, Molecular; D053472:Nod Signaling Adaptor Proteins / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D008024:Ligands; D053472:Nod Signaling Adaptor Proteins; D003960:Diaminopimelic Acid; C034331:N(2)-(gamma-D-glutamyl)-meso-2,2'-diaminopimelic acid