ArticleThe Biochemical journal2013
Dynamic conformational switching in the chemokine ligand is essential for G-protein-coupled receptor activation.
Article in The Biochemical journal, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 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
19 citing papers in PubMed, 26 citations in OpenAlex.
- Structure basis for C-C chemokine receptor 4 modulation by orthosteric and allosteric antagonists.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Heterodimers Are an Integral Component of Chemokine Signaling Repertoire.International journal of molecular sciences · 2023Review
- Latest update on chemokine receptors as therapeutic targets.Biochemical Society transactions · 2021Review
- A highly efficient method for the production and purification of recombinant human CXCL8.PloS one · 2021Article
- Article
- Article
- Structural basis of chemokine and receptor interactions: Key regulators of leukocyte recruitment in inflammatory responses.Protein science : a publication of the Protein Society · 2020Review
- How do chemokines navigate neutrophils to the target site: Dissecting the structural mechanisms and signaling pathways.Cellular signalling · 2019Review
- Biased Signaling of CCL21 and CCL19 Does Not Rely on N-Terminal Differences, but Markedly on the Chemokine Core Domains and Extracellular Loop 2 of CCR7.Frontiers in immunology · 2019Article
- Dynamics-Derived Insights into Complex Formation between the CXCL8 Monomer and CXCR1 N-Terminal Domain: An NMR Study.Molecules (Basel, Switzerland) · 2018Article
- Glycosaminoglycan Interactions Fine-Tune Chemokine-Mediated Neutrophil Trafficking: Structural Insights and Molecular Mechanisms.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2018Review
- Chemokine Signaling and the Regulation of Bidirectional Leukocyte Migration in Interstitial Tissues.Cell reports · 2017Article
- Structural Basis of Native CXCL7 Monomer Binding to CXCR2 Receptor N-Domain and Glycosaminoglycan Heparin.International journal of molecular sciences · 2017Article
- Platelet-Derived Chemokine CXCL7 Dimer Preferentially Exists in the Glycosaminoglycan-Bound Form: Implications for Neutrophil-Platelet Crosstalk.Frontiers in immunology · 2017Article
- New paradigms in chemokine receptor signal transduction: Moving beyond the two-site model.Biochemical pharmacology · 2016Review
- CXCL1/MGSA Is a Novel Glycosaminoglycan (GAG)-binding Chemokine: STRUCTURAL EVIDENCE FOR TWO DISTINCT NON-OVERLAPPING BINDING DOMAINS.The Journal of biological chemistry · 2016Article
- Solution NMR characterization of WT CXCL8 monomer and dimer binding to CXCR1 N-terminal domain.Protein science : a publication of the Protein Society · 2015Article
- Characterization of G protein coupling mediated by the conserved D134(3.49) of DRY motif, M241(6.34), and F251(6.44) residues on human CXCR1.FEBS open bio · 2015Article
- Solution structure of CXCL5--a novel chemokine and adipokine implicated in inflammation and obesity.PloS one · 2014Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Chemokines mediate diverse functions from organogenesis to mobilizing leucocytes, and are unusual agonists for class-A GPCRs (G-protein-coupled receptors) because of their large size and multi-domain structure. The current model for receptor activation, which involves interactions between chemokine N-loop and receptor N-terminal residues (Site-I) and between chemokine N-terminal and receptor extracellular loop/transmembrane residues (Site-II), fails to describe differences in ligand/receptor selectivity and the activation of multiple signalling pathways. In the present study, we show in neutrophil-activating chemokine CXCL8 that the highly conserved GP (glycine-proline) motif located distal to both N-terminal and N-loop residues couples Site-I and Site-II interactions. GP mutants showed large differences from native-like to complete loss of function that could not be correlated with the specific mutation, receptor affinity or subtype, or a specific signalling pathway. NMR studies indicated that the GP motif does not influence Site-I interactions, but molecular dynamics simulations suggested that this motif dictates substates of the CXCL8 conformational ensemble. We conclude that the GP motif enables diverse receptor functions by controlling cross-talk between Site-I and Site-II, and further propose that the repertoire of chemokine functions is best described by a conformational ensemble model in which a network of long-range coupled indirect interactions mediate receptor activity.
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What OpenQuestion holds
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.