The Innate Immune Protein Nod2 Binds Directly to MDP, a Bacterial Cell Wall Fragment

Grimes, Catherine L.; Ariyananda, Lushanti De Zoysa; Melnyk, James E.; O’Shea, Erin K.

doi:10.1021/ja303883c

Cited by 174 publications

(204 citation statements)

References 31 publications

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“…Rather than refuting the importance of the LRRs, this observation may reflect a need for the nucleotide-binding domain to facilitate proper folding of the NOD2 LRRs. Simultaneously, surface plasmon resonance studies reported direct binding between NOD2 and MDP (Grimes et al, 2012). Confirming the need PRRs in Health and Disease for further studies to characterize the precise nature of the interaction of NOD2 with MDP, this work reported competitive binding, at nanomolar affinities, for both the agonist and antagonist stereoisomers of MDP with NOD2.…”

Section: Activation and Signal Transduction In The Nucleotide-bindsupporting

confidence: 72%

International Union of Basic and Clinical Pharmacology. XCVI. Pattern Recognition Receptors in Health and Disease

et al. 2015

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Section: Activation and Signal Transduction In The Nucleotide-bindsupporting

confidence: 72%

International Union of Basic and Clinical Pharmacology. XCVI. Pattern Recognition Receptors in Health and Disease

et al. 2015

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“…In contrast, NOD2 recognizes MDP, a PGN fragment that is found in Gram-negative and Grampositive bacteria alike (34) ( Table 1). The LRR region of NOD1 or NOD2 is essential for PGN detection (33,106), and recent evidence has revealed direct binding of these domains to PGN fragments (37,62,77). It is thought that direct binding of MDP or ieDAP leads to a conformational change of the LRR horseshoe structure and to homodimerization of the NLR via the NOD domain (56, 100).…”

Section: Noncanonical Inflammasomes and Intracellular Lps Sensingmentioning

confidence: 99%

NOD-Like Receptors: Guardians of Intestinal Mucosal Barriers

2015

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The NOD-like receptors (NLRs) are cytosolic pattern-recognition receptors, which are critically involved in mucosal immune defense. The association of the NLR, NOD2, with inflammatory bowel disease first pointed to the NLRs potential function as guardians of the intestinal barrier. Since then, several studies have emphasized the importance of NLRs in maintaining gut homeostasis and intestinal infections, and in shaping the microbiota. In this review, we will highlight the function of NLRs in intestinal inflammation.

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“…It is involved in the recognition of portions of muramyl dipeptide (MDP; Girardin et al, 2003;Grimes et al, 2012) constituent of the cell wall of Gram-positive and Gram-negative bacteria (Strober et al, 2006).…”

mentioning

confidence: 99%

NOD2 Contributes to Porphyromonas gingivalis–induced Bone Resorption

et al. 2014

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The NOD-like receptors are cytoplasmic proteins that sense microbial by-products released by invasive bacteria. Although NOD1 and NOD2 are functionally expressed in cells from oral tissues and play a role triggering immune responses, the role of NOD2 receptor in the bone resorption and in the modulation of osteoclastogenesis is still unclear. We show that in an experimental model of periodontitis with Porphyromonas gingivalis W83, NOD2-/- mice showed lower bone resorption when compared to wild type. Quantitative polymerase chain reaction analysis revealed that wild-type infected mice showed an elevated RANKL/OPG ratio when compared to NOD2-/- infected mice. Moreover, the expression of 2 osteoclast activity markers—cathepsin K and matrix metalloproteinase 9—was significantly lower in gingival tissue from NOD2-/- infected mice compared to WT infected ones. The in vitro study reported an increase in the expression of the NOD2 receptor 24 hr after stimulation of hematopoietic bone marrow cells with M-CSF and RANKL. We also evaluated the effect of direct activation of NOD2 receptor on osteoclastogenesis, by the activation of this receptor in preosteoclasts culture, with different concentrations of muramyl dipeptide. The results show no difference in the number of TRAP-positive cells. Although it did not alter the osteoclasts differentiation, the activation of NOD2 receptor led to a significant increase of cathepsin K expression. We confirm that this enzyme was active, since the osteoclasts resorption capacity was enhanced by muramyl dipeptide stimulation, evaluated in osteoassay plate. These results show that the lack of NOD2 receptor impairs the bone resorption, suggesting that NOD2 receptor could contribute to the progression of bone resorption in experimental model of periodontitis. The stimulation of NOD2 by its agonist, muramyl dipeptide, did not affect osteoclastogenesis, but it does favor the bone resorption capacity identified by increased osteoclast activity.

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The Innate Immune Protein Nod2 Binds Directly to MDP, a Bacterial Cell Wall Fragment

Cited by 174 publications

References 31 publications

International Union of Basic and Clinical Pharmacology. XCVI. Pattern Recognition Receptors in Health and Disease

International Union of Basic and Clinical Pharmacology. XCVI. Pattern Recognition Receptors in Health and Disease

NOD-Like Receptors: Guardians of Intestinal Mucosal Barriers

NOD2 Contributes to Porphyromonas gingivalis–induced Bone Resorption

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