ArticleBritish journal of pharmacology2012
Small molecule chemokine mimetics suggest a molecular basis for the observation that CXCL10 and CXCL11 are allosteric ligands of CXCR3.
Article in British journal of pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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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.
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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, 45 citations in OpenAlex.
- SOX17-silenced HPAECs upregulate NF-κB-induced CXCL10 and CXCL11: implications for lymphocyte chemotaxis in SOX17-PAH.Scientific reports · 2025Article
- Engineered NIR-Responsive Exosomes for Synergistic Photoimmunotherapy of Hepatocellular Carcinoma.ACS omega · 2025Article
- Cytokine interactions and chemokine dysregulations in mastitis immunopathogenesis: insights from transcriptomic profiling of milk somatic cells in tropical Sahiwal (Frontiers in immunology · 2025Article
- BaNDyT: Bayesian Network modeling of molecular Dynamics Trajectories.bioRxiv : the preprint server for biology · 2024Article
- A review of the pleiotropic actions of the IFN-inducible CXC chemokine receptor 3 ligands in the synovial microenvironment.Cellular and molecular life sciences : CMLS · 2023Review
- A highly efficient method for the production and purification of recombinant human CXCL8.PloS one · 2021Article
- Computational Study of C-X-C Chemokine Receptor (CXCR)3 Binding with Its Natural Agonists Chemokine (C-X-C Motif) Ligand (CXCL)9, 10 and 11 and with Synthetic Antagonists: Insights of Receptor Activation towards Drug Design for Vitiligo.Molecules (Basel, Switzerland) · 2020Article
- Shrunken Pore Syndrome Is Associated With Increased Levels of Atherosclerosis-Promoting Proteins.Kidney international reports · 2019Article
- Chemokines and Chemokine Receptors: Orchestrating Tumor Metastasization.International journal of molecular sciences · 2018Review
- The role of CXCR3/LRP1 cross-talk in the invasion of primary brain tumors.Nature communications · 2017Article
- Structural Analysis of Chemokine Receptor-Ligand Interactions.Journal of medicinal chemistry · 2017Review
- Circulatory Levels of C-X-C Motif Chemokine Ligands 1, 9, and 10 Are Elevated in Patients with Ischemic Stroke.The Eurasian journal of medicine · 2017Article
- Hydrogen Peroxide Triggers a Dual Signaling Axis To Selectively Suppress Activated Human T Lymphocyte Migration.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- Mutational Analysis of Atypical Chemokine Receptor 3 (ACKR3/CXCR7) Interaction with Its Chemokine Ligands CXCL11 and CXCL12.The Journal of biological chemistry · 2017Article
- Functional inhibition of chemokine receptor CCR2 by dicer-substrate-siRNA prevents pain development.Molecular pain · 2016Article
- CXCR3 antagonist VUF10085 binds to an intrahelical site distinct from that of the broad spectrum antagonist TAK-779.British journal of pharmacology · 2015Article
- Distinct conformations of the chemokine receptor CCR4 with implications for its targeting in allergy.Journal of immunology (Baltimore, Md. : 1950) · 2014Article
- Critical analysis of the successes and failures of homology models of G protein-coupled receptors.Proteins · 2013Article
- CXCR3-dependent recruitment and CCR6-mediated positioning of Th-17 cells in the inflamed liver.Journal of hepatology · 2012Article
- The yin and yang of chemokine receptor activation.British journal of pharmacology · 2012Article
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Authors and funding
12 authors at 6 institutions in 3 countries.
Funding
Abstract
background and purposeThe chemokine receptor CXCR3 directs migration of T-cells in response to the ligands CXCL9/Mig, CXCL10/IP-10 and CXCL11/I-TAC. Both ligands and receptors are implicated in the pathogenesis of inflammatory disorders, including atherosclerosis and rheumatoid arthritis. Here, we describe the molecular mechanism by which two synthetic small molecule agonists activate CXCR3. EXPERIMENTAL APPROACH: As both small molecules are basic, we hypothesized that they formed electrostatic interactions with acidic residues within CXCR3. Nine point mutants of CXCR3 were generated in which an acidic residue was mutated to its amide counterpart. Following transient expression, the ability of the constructs to bind and signal in response to natural and synthetic ligands was examined. KEY
resultsThe CXCR3 mutants D112N, D195N and E196Q were efficiently expressed and responsive in chemotaxis assays to CXCL11 but not to CXCL10 or to either of the synthetic agonists, confirmed with radioligand binding assays. Molecular modelling of both CXCL10 and CXCR3 suggests that the small molecule agonists mimic a region of the '30s loop' (residues 30-40 of CXCL10) which interacts with the intrahelical CXCR3 residue D112, leading to receptor activation. D195 and E196 are located in the second extracellular loop and form putative intramolecular salt bridges required for a CXCR3 conformation that recognizes CXCL10. In contrast, CXCL11 recognition by CXCR3 is largely independent of these residues. CONCLUSION AND IMPLICATIONS: We provide here a molecular basis for the observation that CXCL10 and CXCL11 are allosteric ligands of CXCR3. Such findings may have implications for the design of CXCR3 antagonists.
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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.