ArticleACS chemical biology2017
Membrane Association Dictates Ligand Specificity for the Innate Immune Receptor NOD2.
Article in ACS chemical biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed, 29 citations in OpenAlex.
- Comparing Chemoenzymatic and Conventional Synthetic Strategies to Wall Teichoic Acid Peptidoglycan Fragments.Israel journal of chemistry · 2026Article
- Review
- FOCUS on NOD2: Advancing IBD Drug Discovery with a User-Informed Machine Learning Framework.ACS medicinal chemistry letters · 2024Article
- Small molecule modulators of immune pattern recognition receptors.RSC chemical biology · 2023Review
- A nod to the bond between NOD2 and mycobacteria.PLoS pathogens · 2023Review
- Multifaceted roles and regulation of nucleotide-binding oligomerization domain containing proteins.Frontiers in immunology · 2023Review
- Novel Scaffolds for Modulation of NOD2 Identified by Pharmacophore-Based Virtual Screening.Biomolecules · 2022Article
- ProtectedACS chemical biology · 2021Article
- Bacterial Peptidoglycan Fragments Differentially Regulate Innate Immune Signaling.ACS central science · 2021Article
- Designed leucine-rich repeat proteins bind two muramyl dipeptide ligands.Protein science : a publication of the Protein Society · 2021Article
- Synthesis of Bacterial-Derived Peptidoglycan Cross-Linked Fragments.The Journal of organic chemistry · 2020Article
- Revisiting peptidoglycan sensing: interactions with host immunity and beyond.Chemical communications (Cambridge, England) · 2020Review
- Differential Peptidoglycan Recognition Assay Using Varied Surface Presentations.Journal of the American Chemical Society · 2020Article
- Article
- Peptidoglycan O-Acetylation as a Virulence Factor: Its Effect on Lysozyme in the Innate Immune System.Antibiotics (Basel, Switzerland) · 2019Review
- Synthesis and Application of Methyl N,O-Hydroxylamine Muramyl Peptides.Chembiochem : a European journal of chemical biology · 2019Article
- Modulation of the NOD-like receptors NOD1 and NOD2: A chemist's perspective.Bioorganic & medicinal chemistry letters · 2019Review
- Peptidoglycan Metabolite Photoaffinity Reporters Reveal Direct Binding to Intracellular Pattern Recognition Receptors and Arf GTPases.ACS chemical biology · 2019Article
- Bacterial Derived Carbohydrates Bind Cyr1 and Trigger Hyphal Growth in Candida albicans.ACS infectious diseases · 2018Article
- Crohn's Disease Variants of Nod2 Are Stabilized by the Critical Contact Region of Hsp70.Biochemistry · 2017Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The human gut must regulate its immune response to resident and pathogenic bacteria, numbering in the trillions. The peptidoglycan component of the bacterial cell wall is a dense and rigid structure that consists of polymeric carbohydrates and highly cross-linked peptides which offers protection from the host and surrounding environment. Nucleotide-binding oligomerization domain-containing protein 2 (NOD2), a human membrane-associated innate immune receptor found in the gut epithelium and mutated in an estimated 30% of Crohn's disease patients, binds to peptidoglycan fragments and initiates an immune response. Using a combination of chemical synthesis, advanced analytical assays, and protein biochemistry, we tested the binding of a variety of synthetic peptidoglycan fragments to wild-type (WT)-NOD2. Only when the protein was presented in the native membrane did binding measurements correlate with a NOD2-dependent nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) response, supporting the hypothesis that the native-membrane environment confers ligand specificity to the NOD2 receptor for NF-κB signaling. While N-acetyl-muramyl dipeptide (MDP) has been thought to be the minimal peptidoglycan fragment necessary to activate a NOD2-dependent immune response, we found that fragments with and without the dipeptide moiety are capable of binding and activating a NOD2-dependent NF-κB response, suggesting that the carbohydrate moiety of the peptidoglycan fragments is the minimal functional epitope. This work highlights the necessity of studying NOD2-ligand binding in systems that resemble the receptor's natural environment, as the cellular membrane and/or NOD2 interacting partners appear to play a crucial role in ligand binding and in triggering an innate immune response.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.