ArticleACS chemical biology2019
Peptidoglycan Metabolite Photoaffinity Reporters Reveal Direct Binding to Intracellular Pattern Recognition Receptors and Arf GTPases.
Article in ACS chemical biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 40 citations in OpenAlex.
- Bifunctional Monosaccharides Preferentially Localize to Nuclear Subcompartments.Chembiochem : a European journal of chemical biology · 2026Article
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- Photocrosslinking and capture for the analysis of carbohydrate-dependent interactions.Bioorganic & medicinal chemistry letters · 2025Review
- Mechanisms conferring bacterial cell wall variability and adaptivity.Biochemical Society transactions · 2024Review
- Monitoring host-pathogen interactions using chemical proteomics.RSC chemical biology · 2024Review
- Small molecule modulators of immune pattern recognition receptors.RSC chemical biology · 2023Review
- Synthesis and validation of click-modified NOD1/2 agonists.Innate immunity · 2023Article
- Role of pattern recognition receptors in sensingHeliyon · 2023Review
- Chemical biology tools for protein labelling: insights into cell-cell communication.The Biochemical journal · 2023Review
- Antimicrobial overproduction sustains intestinal inflammation by inhibiting Enterococcus colonization.Cell host & microbe · 2023Article
- Review
- Identification of Novel Endogenous NOD Ligands: Quantitative Analysis of Binding Affinities of NOD1 or NOD2 with Sphingosine-1-Phosphate Using Microscale Thermophoresis.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Photoaffinity labelling strategies for mapping the small molecule-protein interactome.Organic & biomolecular chemistry · 2021Review
- Evaluation of fully-functionalized diazirine tags for chemical proteomic applications.Chemical science · 2021Article
- Bacterial Peptidoglycan Fragments Differentially Regulate Innate Immune Signaling.ACS central science · 2021Article
- ProteinOpen biology · 2021Review
- Revisiting peptidoglycan sensing: interactions with host immunity and beyond.Chemical communications (Cambridge, England) · 2020Review
- NOD1 and NOD2 Activation by Diverse Stimuli: a Possible Role for Sensing Pathogen-Induced Endoplasmic Reticulum Stress.Infection and immunity · 2020Review
- Targeted and proteome-wide analysis of metabolite-protein interactions.Current opinion in chemical biology · 2020Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The peptidoglycan fragments γ-d-glutamyl- meso-diaminopimelic acid (iE-DAP) and muramyl-dipeptide (MDP) are microbial-specific metabolites that activate intracellular pattern recognition receptors and stimulate immune signaling pathways. While extensive structure-activity studies have demonstrated that these bacterial cell wall metabolites trigger NOD1- and NOD2-dependent signaling, their direct binding to these innate immune receptors or other proteins in mammalian cells has not been established. To characterize these fundamental microbial metabolite-host interactions, we synthesized a series of peptidoglycan metabolite photoaffinity reporters and evaluated their cross-linking to NOD1 and NOD2 in mammalian cells. We show that active iE-DAP and MDP photoaffinity reporters selectively cross-linked NOD1 and NOD2, respectively, and not their inactive mutants. We also discovered MDP reporter cross-linking to Arf GTPases, which interacted most prominently with GTP-bound Arf6 and coimmunoprecipitated with NOD2 upon MDP stimulation. Notably, MDP binding to NOD2 and Arf6 was abrogated with loss-of-function NOD2 mutants associated with Crohn's disease. Our studies demonstrate peptidoglycan metabolite photoaffinity reporters can capture their cognate immune receptors in cells and reveal unpredicted ligand-induced interactions with other cellular cofactors. These photoaffinity reporters should afford useful tools to discover and characterize other peptidoglycan metabolite-interacting proteins.
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Registered trials
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