ArticleThe Journal of biological chemistry2014
Engagement of nucleotide-binding oligomerization domain-containing protein 1 (NOD1) by receptor-interacting protein 2 (RIP2) is insufficient for signal transduction.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 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
17 citing papers in PubMed, 29 citations in OpenAlex.
- Structural and dynamic basis of NOD2 tandem CARD association and NOD1/2-RIP2 signaling complexes.PLoS computational biology · 2026Article
- Current advances on RIPK2 and its inhibitors in pathological processes: a comprehensive review.Frontiers in molecular neuroscience · 2025Review
- C-type lectin 4 of Toxocara canis activates NF-ĸB and MAPK pathways by modulating NOD1/2 and RIP2 in murine macrophages in vitro.Parasitology research · 2024Article
- Discovery of Pyrazolocarboxamides as Potent and Selective Receptor Interacting Protein 2 (RIP2) Kinase Inhibitors.ACS medicinal chemistry letters · 2019Article
- XIAP controls RIPK2 signaling by preventing its deposition in speck-like structures.Life science alliance · 2019Article
- NOD Signaling and Cell Death.Frontiers in cell and developmental biology · 2019Review
- Sequence-based structural analysis and evaluation of polymorphism in buffalo Nod-like receptor-1 gene.3 Biotech · 2019Article
- Structural basis of RIP2 activation and signaling.Nature communications · 2018Article
- The Role of Nucleotide-Binding Oligomerization Domain-Like Receptors in Pulmonary Infection.American journal of respiratory cell and molecular biology · 2017Review
- NOD1CARD Might Be Using Multiple Interfaces for RIP2-Mediated CARD-CARD Interaction: Insights from Molecular Dynamics Simulation.PloS one · 2017Article
- Role of nucleotide-binding oligomerization domain 1 (NOD1) and its variants in human cytomegalovirus control in vitro and in vivo.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Article
- Inflammatory Signaling by NOD-RIPK2 Is Inhibited by Clinically Relevant Type II Kinase Inhibitors.Chemistry & biology · 2015Article
- International Union of Basic and Clinical Pharmacology. XCVI. Pattern recognition receptors in health and disease.Pharmacological reviews · 2015Review
- Dysfunctional Crohn's Disease-Associated NOD2 Polymorphisms Cannot be Reliably Predicted on the Basis of RIPK2 Binding or Membrane Association.Frontiers in immunology · 2015Article
- Article
- Insights into the molecular basis of the NOD2 signalling pathway.Open biology · 2014Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Following activation, the cytoplasmic pattern recognition receptor nucleotide-binding oligomerization domain-containing protein 1 (NOD1) interacts with its adaptor protein receptor-interacting protein 2 (RIP2) to propagate immune signaling and initiate a proinflammatory immune response. This interaction is mediated by the caspase recruitment domain (CARD) of both proteins. Polymorphisms in immune proteins can affect receptor function and predispose individuals to specific autoinflammatory disorders. In this report, we show that mutations in helix 2 of the CARD of NOD1 disrupted receptor function but did not interfere with RIP2 interaction. In particular, N43S, a rare polymorphism, resulted in receptor dysfunction despite retaining normal cellular localization, protein folding, and an ability to interact with RIP2. Mutation of Asn-43 resulted in an increased tendency to form dimers, which we propose is the source of this dysfunction. We also demonstrate that mutation of Lys-443 and Tyr-474 in RIP2 disrupted the interaction with NOD1. Mapping the key residues involved in the interaction between NOD1 and RIP2 to the known structures of CARD complexes revealed the likely involvement of both type I and type III interfaces in the NOD1·RIP2 complex. Overall we demonstrate that the NOD1-RIP2 signaling axis is more complex than previously assumed, that simple engagement of RIP2 is insufficient to mediate signaling, and that the interaction between NOD1 and RIP2 constitutes multiple CARD-CARD interfaces.
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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.