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

Sahoo, Bikash R.; Swain, Bichitrananda; Dikhit, Manas Ranjan; Basu, Madhubanti; Bej, Aritra; Jayasankar, P.; Samanta, Mrinal

doi:10.1007/s12010-013-0263-6

Cited by 23 publications

(18 citation statements)

References 45 publications

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“…The techniques of homology modeling, molecular docking, and MD simulations are being increasingly used to study the molecular interactions between key proteins of innate immune system. For instance, in silico studies have been carried out to study the interactions of TLR2 with peptidoglycans (Lipoteichoic Acid and Zymosan Ligands) and downstream MyD88 adaptor protein (Sahoo et al ., ), the interaction between TLR3 and dsRNA (poly I:C) (Sahoo et al ., ), binding modes of iE‐DAP on NOD1 (Sahoo et al ., ), and MDP recognition by NOD2 (Maharana et al ., ). In addition, molecular modeling studies were performed to characterize the potential homo‐dimer interface between TLR8 subunits and interaction with the antiviral drug R848 (Govindaraj et al ., ); the homo and hetero‐dimerization between TLR10, TRL1, and TLR2 (Govindaraj et al ., ); and the mechanism of inhibition of TLR signaling pathway by a membrane bound protein ST2L (Basith et al ., ).…”

Section: Resultsmentioning

confidence: 99%

Structural insights into the MDP binding and CARD-CARD interaction in zebrafish (Danio rerio) NOD2: a molecular dynamics approach

Maharana

Patra

et al. 2014

J. Mol. Recognit.

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Nucleotide binding and oligomerization domain (NOD2) is a key component of innate immunity that is highly specific for muramyl dipeptide (MDP)-a peptidoglycan component of bacterial cell wall. MDP recognition by NOD2-leucine rich repeat (LRR) domain activates NF-κB signaling through a protein-protein interaction between caspase activating and recruitment domains (CARDs) of NOD2 and downstream receptor interacting and activating protein kinase 2 (RIP2). Due to the lack of crystal/NMR structures, MDP recognition and CARD-CARD interaction are poorly understood. Herein, we have predicted the probable MDP and CARD-CARD binding surfaces in zebrafish NOD2 (zNOD2) using various in silico methodologies. The results show that the conserved residues Phe819, Phe871, Trp875, Trp929, Trp899, and Arg845 located at the concave face of zNOD2-LRR confer MDP recognition by hydrophobic and hydrogen bond (H-bond) interactions. Molecular dynamics simulations reveal a stable association between the electropositive surface on zNOD2-CARDa and the electronegative surface on zRIP2-CARD reinforced mostly by H-bonds and electrostatic interactions. Importantly, a 3.5 Å salt bridge is observed between Arg60 of zNOD2-CARDa and Asp494 of zRIP2-CARD. Arg11 and Lys53 of zNOD2-CARDa and Ser498 and Glu508 of zRIP2-CARD are critical residues for CARD-CARD interaction and NOD2 signaling. The 2.7 Å H-bond between Lys104 of the linker and Glu508 of zRIP2-CARD suggests a possible role of the linker for shaping CARD-CARD interaction. These findings are consistent with existing mutagenesis data. We provide first insight into MDP recognition and CARD-CARD interaction in the zebrafish that will be useful to understand the molecular basis of NOD signaling in a broader perspective.

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Section: Resultsmentioning

confidence: 99%

Structural insights into the MDP binding and CARD-CARD interaction in zebrafish (Danio rerio) NOD2: a molecular dynamics approach

Maharana

Patra

et al. 2014

J. Mol. Recognit.

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“…Recent studies indicate NOD2, not NOD1, is involved in pathogenesis of DN. NOD2 was upregulated in HFD-induced and STZinduced diabetic mice, and in kidney biopsy samples from patients with type 2 diabetes [31]. NOD2 was upregulated in podocytes treated with high glucose, AGEs, TNF-β, and Nod2 − / − mice were protected from hyperglycemia-induced reduction in nephrin expression [32,33].…”

Section: Discussionmentioning

confidence: 98%

High Glucose and Lipopolysaccharide Activate NOD1- RICK-NF-κB Inflammatory Signaling in Mesangial Cells

Huang

Gou

Long

et al. 2016

Exp Clin Endocrinol Diabetes

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Systemic and local low-grade inflammation and release of proinflammatory cytokines are implicated in the development and progression of diabetes mellitus (DM) and diabetic nephropathy (DN). The TLR2, TLR4, and NLRP3 inflammasomes of the innate immune system produce various proinflammatory cytokines and are critically involved in inflammatory responses in kidney tissues. The NOD-like receptor (NLR) NOD1 is involved in the NF-κB inflammatory signaling pathway and has an important role in the development of insulin resistance. Extracellular stimuli such as high glucose or lipopolysaccharide (LPS) can induce NOD1-RICK to activate NF-κB, which is associated with diabetes and other chronic inflammatory conditions. It is currently unknown whether NOD1-RICK-mediated NF-κB signaling is involved in DN pathogenesis. In this study, expression of NOD1, RICK, IκBα, NF-κB and IL-1β was detected in cultured rat glomerular mesangial cells (rGMCs) stimulated with high concentrations of glucose and LPS. ML130, a NOD1 inhibitor, was used to investigate the role of the NOD1 signaling pathway in DN inflammation. Our results showed that high glucose or LPS increased the protein and mRNA expression of NOD1, RICK,NF-κBp65 and IL-1β, but attenuated IκBα expression (<0.05). These changes were synergistically enhanced by stimulating with high glucose and LPS. However, pretreatment with the NOD1 inhibitor ML130 significantly reversed these changes (<0.05). These combined results support the hypothesis that high glucose and LPS can activate the NOD1-RICK-NF-κB inflammatory signaling pathway via the NOD1 receptor, and may participate in the development of DN.

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“…Previously, advanced techniques like ab-initio modeling [ 100 ] and protein threading [ 101 ] that employ a multi-template modeling approach was used to construct reliable 3D-model structures for rohu NOD1 and NOD2 LRR domains ( Fig. 3 ) due to the unavailability of an experimental structure for NOD receptor [ 102 , 103 ]. However, at present the BLASTp search of rohu NOD1 LRR against PDB data bank resulted four hits that include the PDB IDs: 5IRM (34.66% identity), 5IRL (34.66% identity), 4R5D (29.63% identity) and 4R6G (28.64% identity).…”

Section: Comparative Tertiary Structure Modeling Of Fish Tlrs/nlrsmentioning

confidence: 99%

Structure of fish Toll-like receptors (TLR) and NOD-like receptors (NLR)

Sahoo

2020

International Journal of Biological Macromolecules

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124

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Innate immunity driven by pattern recognition receptor (PRR) protects the host from invading pathogens. Aquatic animals like fish where the adaptive immunity is poorly developed majorly rely on their innate immunity modulated by PRRs like toll-like receptors (TLR) and NOD-like receptors (NLR). However, current development to improve the fish immunity via TLR/NLR signaling is affected by a poor understanding of its mechanistic and structural features. This review discusses the structure of fish TLRs/NLRs and its interaction with pathogen associated molecular patterns (PAMPs) and downstream signaling molecules. Over the past one decade, significant progress has been done in studying the structure of TLRs/NLRs in higher eukaryotes; however, structural studies on fish innate immune receptors are undermined. Several novel TLR genes are identified in fish that are absent in higher eukaryotes, but the function is still poorly understood. Unlike the fundamental progress achieved in developing antagonist/agonist to modulate human innate immunity, analogous studies in fish are nearly lacking due to structural inadequacy. This underlies the importance of exploring the structural and mechanistic details of fish TLRs/NLRs at an atomic and molecular level. This review outlined the mechanistic and structural basis of fish TLR and NLR activation.

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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

Cited by 23 publications

References 45 publications

Structural insights into the MDP binding and CARD-CARD interaction in zebrafish (Danio rerio) NOD2: a molecular dynamics approach

Structural insights into the MDP binding and CARD-CARD interaction in zebrafish (Danio rerio) NOD2: a molecular dynamics approach

High Glucose and Lipopolysaccharide Activate NOD1- RICK-NF-κB Inflammatory Signaling in Mesangial Cells

Structure of fish Toll-like receptors (TLR) and NOD-like receptors (NLR)

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