ArticleScience signaling2019
Kinetics of CXCL12 binding to atypical chemokine receptor 3 reveal a role for the receptor N terminus in chemokine binding.
Article in Science signaling, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 49 citations in OpenAlex.
- Atomic, structural and molecular insights into GPCR ligand binding and signalling.Nature reviews. Molecular cell biology · 2026Review
- Elevated conformational dynamics makes ACKR3 activation-prone and G protein-incompetent.bioRxiv : the preprint server for biology · 2026Article
- Molecular basis of CXC chemokine receptor 3 ligand multispecificity.Science advances · 2026Article
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- Structural insights into CXCR4 modulation and oligomerization.Nature structural & molecular biology · 2025Article
- Regulation of the chemokine receptors CXCR4 and ACKR3 by receptor activity-modifying proteins.The Journal of biological chemistry · 2025Article
- Essential strategies for the detection of constitutive and ligand-dependent Gi-directed activity of 7TM receptors using bioluminescence resonance energy transfer.bioRxiv : the preprint server for biology · 2024Article
- Interaction and dynamics of chemokine receptor CXCR4 binding with CXCL12 and hBD-3.Communications chemistry · 2024Article
- Atypical Chemokine Receptor 3 "Senses" CXC Chemokine Receptor 4 Activation Through GPCR Kinase Phosphorylation.Molecular pharmacology · 2023Article
- Discovery and pharmacophoric characterization of chemokine network inhibitors using phage-display, saturation mutagenesis and computational modelling.Nature communications · 2023Article
- ACKR3-arrestin2/3 complexes reveal molecular consequences of GRK-dependent barcoding.bioRxiv : the preprint server for biology · 2023Article
- Atypical Chemokine Receptor 3 'Senses' CXC Chemokine Receptor 4 Activation Through GPCR Kinase Phosphorylation.bioRxiv : the preprint server for biology · 2023Article
- The chemokines CXCL8 and CXCL12: molecular and functional properties, role in disease and efforts towards pharmacological intervention.Cellular & molecular immunology · 2023Review
- Prospects for targeting ACKR1 in cancer and other diseases.Frontiers in immunology · 2023Review
- Targeting CXCR4 and CD47 Receptors: An Overview of New and Old Molecules for a Biological Personalized Anticancer Therapy.International journal of molecular sciences · 2022Review
- Effects of Small Molecule Ligands on ACKR3 Receptors.Molecular pharmacology · 2022Article
- Structures of atypical chemokine receptor 3 reveal the basis for its promiscuity and signaling bias.Science advances · 2022Article
- CXCR4/CXCL12 Activities in the Tumor Microenvironment and Implications for Tumor Immunotherapy.Cancers · 2022Review
- A Scintillation Proximity Assay for Real-Time Kinetic Analysis of Chemokine-Chemokine Receptor Interactions.Cells · 2022Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Chemokines bind to membrane-spanning chemokine receptors, which signal through G proteins and promote cell migration. However, atypical chemokine receptor 3 (ACKR3) does not appear to couple to G proteins, and instead of directly promoting cell migration, it regulates the extracellular concentration of chemokines that it shares with the G protein-coupled receptors (GPCRs) CXCR3 and CXCR4, thereby influencing the responses of these receptors. Understanding how these receptors bind their ligands is important for understanding these different processes. Here, we applied association and dissociation kinetic measurements coupled to β-arrestin recruitment assays to investigate ACKR3:chemokine interactions. Our results showed that CXCL12 binding is unusually slow and driven by the interplay between multiple binding epitopes. We also found that the amino terminus of the receptor played a key role in chemokine binding and activation by preventing chemokine dissociation. It was thought that chemokines initially bind receptors through interactions between the globular domain of the chemokine and the receptor amino terminus, which then guides the chemokine amino terminus into the transmembrane pocket of the receptor to initiate signaling. On the basis of our kinetic data, we propose an alternative mechanism in which the amino terminus of the chemokine initially forms interactions with the extracellular loops and transmembrane pocket of the receptor, which is followed by the receptor amino terminus wrapping around the core of the chemokine to prolong its residence time. These data provide insight into how ACKR3 competes and cooperates with canonical GPCRs in its function as a scavenger receptor.
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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.