ArticleScience advances2022
Structures of atypical chemokine receptor 3 reveal the basis for its promiscuity and signaling bias.
Article in Science advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 80 citations in OpenAlex.
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- Identification of Entacapone as a Novel β-Arrestin 1 Biased Antagonist of CXCR7.Molecules (Basel, Switzerland) · 2026Article
- Chemokine receptor activity is differentially regulated by membrane cholesterol.bioRxiv : the preprint server for biology · 2026Article
- β-arrestin recruitment facilitates a direct association with G proteins.Nature communications · 2026Article
- Elevated conformational dynamics makes ACKR3 activation-prone and G protein-incompetent.bioRxiv : the preprint server for biology · 2026Article
- Pharmacological modulation of CXCL12/CXCR4/ACKR3 for brain disorders - an overview.Cell communication and signaling : CCS · 2026Review
- Molecular basis of CXC chemokine receptor 3 ligand multispecificity.Science advances · 2026Article
- Atypical GPCR Activation Resolved by Nanobody Engineering.bioRxiv : the preprint server for biology · 2026Article
- The CXCL12-CXCR4 axis in colorectal cancer: immune regulation, metastatic progression, and therapeutic implications.Frontiers in immunology · 2026Review
- Constitutive activity of an atypical chemokine receptor revealed by inverse agonistic nanobodies.Nature communications · 2025Article
- Targeting the CXCL12/CXCR4 pathway by an optimized derivative or EPI-X4 preserves chondrocyte function and offers a novel therapeutic approach in rheumatic diseases.Arthritis research & therapy · 2025Article
- Inhibition of constitutive activity of the atypical chemokine receptor 3 by the small-molecule inverse agonist VUF16840.Molecular pharmacology · 2025Article
- Rules of engagement: Determinants of chemokine receptor activation and selectivity by CCL27 and CCL28.The Journal of biological chemistry · 2025Article
- Exploring the influence of sex and age on the quality and flavor of Huai goat longissimus thoracis et lumborum through transcriptomic and metabolomic analyses.BMC genomics · 2025Article
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- Encoding and decoding selectivity and promiscuity in the human chemokine-GPCR interaction network.Cell · 2025Article
- Signal termination of the chemokine receptor CCR9 is governed by an arrestin-independent phosphorylation mechanism.The Journal of biological chemistry · 2025Article
- Article
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Authors and funding
11 authors at 6 institutions in 3 countries.
Funding
Abstract
Both CXC chemokine receptor 4 (CXCR4) and atypical chemokine receptor 3 (ACKR3) are activated by the chemokine CXCL12 yet evoke distinct cellular responses. CXCR4 is a canonical G protein-coupled receptor (GPCR), whereas ACKR3 is intrinsically biased for arrestin. The molecular basis for this difference is not understood. Here, we describe cryo-EM structures of ACKR3 in complex with CXCL12, a more potent CXCL12 variant, and a small-molecule agonist. The bound chemokines adopt an unexpected pose relative to those established for CXCR4 and observed in other receptor-chemokine complexes. Along with functional studies, these structures provide insight into the ligand-binding promiscuity of ACKR3, why it fails to couple to G proteins, and its bias toward β-arrestin. The results lay the groundwork for understanding the physiological interplay of ACKR3 with other GPCRs.
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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.