ArticleThe Journal of biological chemistry2019
Evaluation and extension of the two-site, two-step model for binding and activation of the chemokine receptor CCR1.
Article in The Journal of biological chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- Dual-target mu opioid-dopamine DEuropean journal of medicinal chemistry · 2026Article
- The structure of the dopamine DScience advances · 2026Article
- Noncanonical roles of chemokine regions in CCR9 activation revealed by structural modeling and mutational mapping.Nature communications · 2025Article
- Progress in structure-based drug development targeting chemokine receptors.Frontiers in pharmacology · 2025Review
- Chemokine Receptor N-Terminus Charge Dictates Reliance on Post-Translational Modifications for Effective Ligand Capture and Following Boosting by Defense Peptides.International journal of molecular sciences · 2024Article
- Loss of CCL28 and CXCL17 Expression and Increase in CCR1 Expression May Be Related to Malignant Transformation of LGBLEL into Lymphoma.Current issues in molecular biology · 2024Article
- Structural perspectives on chemokine receptors.Biochemical Society transactions · 2024Review
- Pharmacological and Physicochemical Properties Optimization for Dual-Target Dopamine DJournal of medicinal chemistry · 2023Article
- Heterodimers Are an Integral Component of Chemokine Signaling Repertoire.International journal of molecular sciences · 2023Review
- Cryo-EM structure of the human chemerin receptor 1-Gi protein complex bound to the C-terminal nonapeptide of chemerin.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- "Glyco-sulfo barcodes" regulate chemokine receptor function.Cellular and molecular life sciences : CMLS · 2023Article
- Identification and mechanism of G protein-biased ligands for chemokine receptor CCR1.Nature chemical biology · 2022Article
- Selective Boosting of CCR7-Acting Chemokines; Short Peptides Boost Chemokines with Short Basic Tails, Longer Peptides Boost Chemokines with Long Basic Tails.International journal of molecular sciences · 2022Article
- A model of the innate immune response to SARS-CoV-2 in the alveolar epithelium.Royal Society open science · 2021Article
- Behavior of Chemokine Receptor 6 (CXCR6) in Complex with CXCL16 Soluble form Chemokine by Molecular Dynamic Simulations: General Protein‒Ligand Interaction Model and 3D-QSAR Studies of Synthetic Antagonists.Life (Basel, Switzerland) · 2021Article
- Submolecular probing of the complement C5a receptor-ligand binding reveals a cooperative two-site binding mechanism.Communications biology · 2020Article
- 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
- Structural basis of chemokine and receptor interactions: Key regulators of leukocyte recruitment in inflammatory responses.Protein science : a publication of the Protein Society · 2020Review
- Proteolytic chemokine cleavage as a regulator of lymphocytic infiltration in solid tumors.Cancer metastasis reviews · 2019Review
- Influence of Chemokine N-Terminal Modification on Biased Agonism at the Chemokine Receptor CCR1.International journal of molecular sciences · 2019Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Interactions between secreted immune proteins called chemokines and their cognate G protein-coupled receptors regulate the trafficking of leukocytes in inflammatory responses. The two-site, two-step model describes these interactions. It involves initial binding of the chemokine N-loop/β3 region to the receptor's N-terminal region and subsequent insertion of the chemokine N-terminal region into the transmembrane helical bundle of the receptor concurrent with receptor activation. Here, we test aspects of this model with C-C motif chemokine receptor 1 (CCR1) and several chemokine ligands. First, we compared the chemokine-binding affinities of CCR1 with those of peptides corresponding to the CCR1 N-terminal region. Relatively low affinities of the peptides and poor correlations between CCR1 and peptide affinities indicated that other regions of the receptor may contribute to binding affinity. Second, we evaluated the contributions of the two CCR1-interacting regions of the cognate chemokine ligand CCL7 (formerly monocyte chemoattractant protein-3 (MCP-3)) using chimeras between CCL7 and the non-cognate ligand CCL2 (formerly MCP-1). The results revealed that the chemokine N-terminal region contributes significantly to binding affinity but that differences in binding affinity do not completely account for differences in receptor activation. On the basis of these observations, we propose an elaboration of the two-site, two-step model-the "three-step" model-in which initial interactions of the first site result in low-affinity, nonspecific binding; rate-limiting engagement of the second site enables high-affinity, specific binding; and subsequent conformational rearrangement gives rise to receptor activation.
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Registered trials
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