ArticleNature2015
Structural basis of CpG and inhibitory DNA recognition by Toll-like receptor 9.
Article in Nature, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 199 papers.
What it found
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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
199 citing papers in PubMed, 355 citations in OpenAlex.
- Autologous tumor cell vaccine induces antitumor T cell immune responses in patients with mantle cell lymphoma: A phase I/II trial.The Journal of experimental medicine · 2020Trial
- Toll-like receptor 9-overexpressing red blood cell biomimetic microbubbles adsorb cell-free DNA to relieve steatotic liver ischemia-reperfusion injury.Materials today. Bio · 2026Article
- Immunofunctions of Protein and Carbohydrate Assemblies Modulated by Structures Acrossing Scales as Biomaterials.Advanced materials (Deerfield Beach, Fla.) · 2026Review
- Insights into human TLR9 structural dynamics and recognition of pathogen-associated CpG DNA using molecular dynamics simulation.iScience · 2026Article
- Conformationally Constrained Phosphonate Backbone Linkages Enhance CpG Oligonucleotide Activation of Toll-Like Receptor 9.ACS pharmacology & translational science · 2026Article
- Review
- Modular nucleic acid-based construct for delivery of immunostimulatory agonists and oncogene-silencing oligonucleotides in tumours.Nature biomedical engineering · 2026Article
- Rational design of topology-defined DNA nanoframeworks for antigen delivery and cross-presentation.Journal of nanobiotechnology · 2026Article
- α-Synuclein aggregates induce mitochondrial damage and trigger innate immunity to drive neuron-microglia communication.Nature communications · 2026Article
- LNP-based delivery of a Toll-like receptor 9 agonist elicits potent adjuvant effects and antitumor immunity.NPJ vaccines · 2026Article
- Mitochondrial DNA regulation of hepatic ischemia-reperfusion injury and intervention strategies.Journal of translational medicine · 2026Review
- Engineering polymeric RNA scaffolds as programmable combinatorial innate immune agonists.Nucleic acids research · 2026Article
- Deaths in gene therapy of Duchenne muscular dystrophy and other diseases: Underlying mechanisms and mitigating strategies.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Review
- Strategies for Evading Cellular Immunity Against Recombinant AAV Vectors in Gene Therapy.Current medical science · 2026Review
- The magnitude and durability of neutralizing antibody responses to human papillomavirus vaccine do not depend on DNA sensing pathways.Journal of virology · 2026Article
- TLR9-activating cholesterol azetidine derivative-assisted therapeutic vaccines for cancer immunotherapy.Science advances · 2026Article
- Cross-kingdom microbial interactions in the gut during inflammatory bowel disease.Journal of translational medicine · 2026Review
- Cutaneous-Tropism Viruses: Unraveling Pathogenetic Mechanisms and Immunoprophylactic Strategies.Life (Basel, Switzerland) · 2026Review
- Toll-like receptors in innate immunity and inflammation: from fundamental biology to clinic insights.Immunity & inflammation · 2026Review
- Mechanisms of and mitigating strategies for cellular immune responses to CRISPR-associated nucleases in genome editing therapy.Frontiers in medicine · 2026Review
139 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Innate immunity serves as the first line of defence against invading pathogens such as bacteria and viruses. Toll-like receptors (TLRs) are examples of innate immune receptors, which sense specific molecular patterns from pathogens and activate immune responses. TLR9 recognizes bacterial and viral DNA containing the cytosine-phosphate-guanine (CpG) dideoxynucleotide motif. The molecular basis by which CpG-containing DNA (CpG-DNA) elicits immunostimulatory activity via TLR9 remains to be elucidated. Here we show the crystal structures of three forms of TLR9: unliganded, bound to agonistic CpG-DNA, and bound to inhibitory DNA (iDNA). Agonistic-CpG-DNA-bound TLR9 formed a symmetric TLR9-CpG-DNA complex with 2:2 stoichiometry, whereas iDNA-bound TLR9 was a monomer. CpG-DNA was recognized by both protomers in the dimer, in particular by the amino-terminal fragment (LRRNT-LRR10) from one protomer and the carboxy-terminal fragment (LRR20-LRR22) from the other. The iDNA, which formed a stem-loop structure suitable for binding by intramolecular base pairing, bound to the concave surface from LRR2-LRR10. This structure serves as an important basis for improving our understanding of the functional mechanisms of TLR9.
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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.