GO:0031727 CCR2 chemokine receptor binding: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0031727 (CCR2 chemokine receptor binding) is a molecular function describing the binding of a ligand to the CCR2 chemokine receptor.
• The principal high-affinity ligand is CCL2 (MCP-1), but other chemokines such as CCL7 and CCL8 also engage CCR2.
• CCR2 binding triggers Gi-protein-coupled signaling that drives monocyte recruitment and inflammation.
• The CCL2-CCR2 axis is a validated therapeutic target in atherosclerosis and cardiovascular disease.
• CCR2 also serves as a host entry receptor for severe fever with thrombocytopenia syndrome virus (SFTSV).
• Fluorescent and allosteric ligands targeting CCR2 enable direct visualization and pharmacological interrogation of this binding event.
Description
GO:0031727, CCR2 chemokine receptor binding, is a molecular function term that describes the selective interaction between a chemokine ligand and the CCR2 receptor. CCR2 is a seven-transmembrane G-protein-coupled receptor expressed on monocytes, macrophages, and T helper cell subsets, and its engagement by ligands such as CCL2 initiates intracellular signaling cascades that control cell migration and inflammatory gene expression. Because this binding event sits at the apex of monocyte recruitment, it is a central node in cardiovascular, metabolic, and infectious disease research. The term is therefore of broad interest to immunologists, virologists, and drug-discovery scientists who need to measure, perturb, or model receptor-ligand engagement. Understanding CCR2 chemokine receptor binding at molecular resolution also informs the design of allosteric modulators and fluorescent probes for imaging immune cell trafficking.
CCR2 chemokine receptor binding At A Glance
| GO ID | GO:0031727 |
|---|---|
| GO term | CCR2 chemokine receptor binding |
| Ontology | molecular_function |
| Synonym | CCR2 chemokine receptor ligand; monocyte chemoattractant protein 1 receptor binding |
| Major function | Binding of chemokine ligands to the CCR2 receptor to initiate downstream signaling |
| Principal ligand | CCL2 (MCP-1), with additional ligands including CCL7 and CCL8 |
| Receptor class | Seven-transmembrane G-protein-coupled receptor (GPCR) |
| Downstream pathway | Gi-protein-coupled signaling leading to monocyte chemotaxis and inflammatory activation |
| Disease relevance | Atherosclerosis, metabolic inflammation, and SFTSV viral entry |
What Is GO:0031727?
CCR2 chemokine receptor binding (GO:0031727) is defined as the binding of a molecule to a CCR2 chemokine receptor. In practice, this molecular function is executed by chemokine ligands such as CCL2 (also called monocyte chemoattractant protein 1, MCP-1), which dock onto the extracellular surface of CCR2 and stabilize an active receptor conformation. The term captures the physical interaction itself rather than downstream signaling, although binding is the obligatory first step for CCR2-mediated signal transduction.
Why Is CCR2 chemokine receptor binding Important in Cell Biology?
CCR2 chemokine receptor binding is important because it is the molecular trigger for monocyte and macrophage recruitment, a process that underlies chronic inflammatory diseases such as atherosclerosis, obesity-related cardiac dysfunction, and metabolic-associated fatty liver disease. Pharmacological or genetic interruption of this binding event reduces lesion formation and inflammation in preclinical models, making it a high-value target for therapeutic development. In addition, CCR2 binding is exploited by pathogens: severe fever with thrombocytopenia syndrome virus uses CCR2 as a host entry receptor, so understanding the binding interface has direct antiviral implications. Finally, the availability of fluorescent and allosteric ligands for CCR2 provides experimental tools to dissect binding kinetics and receptor occupancy in living systems.
• Defines the first molecular step in CCL2-CCR2 signaling that drives monocyte chemotaxis.
• Central to atherosclerosis initiation and progression, where CCL2-CCR2 axis blockade is atheroprotective.
• Contributes to obesity-induced cardiac dysfunction through CCR2-positive macrophage infiltration.
• Implicated in metabolic-associated fatty liver disease via S100A4-positive monocyte-derived macrophages.
• Mediates host cell entry for severe fever with thrombocytopenia syndrome virus.
• Supports pathological T helper cell expansion in rheumatoid arthritis.
• Provides a druggable GPCR interface for small-molecule and allosteric modulator development.
• Enables fluorescent imaging of receptor occupancy and ligand binding in immune cells.
• Links chemokine biology to glioblastoma stem cell maintenance through infiltrating immune cells.
• Serves as a model system for understanding chemokine receptor-ligand structural determinants.
Molecular Mechanism of CCR2 chemokine receptor binding
Ligand recognition and binding interface
In simple terms: The chemokine ligand fits into a pocket on the outside of the CCR2 receptor like a key in a lock.
CCR2 chemokine receptor binding begins with recognition of the chemokine ligand by the receptor N-terminus and extracellular loops. Structural analyses of chemokine receptor-ligand interactions have defined the two-site model in which the chemokine core binds the receptor N-terminus while the chemokine N-terminus inserts into the transmembrane binding pocket to activate the receptor. CCL2 is the prototypical high-affinity ligand for CCR2, and this interaction is the defining event of GO:0031727.
Allosteric modulation and intracellular binding sites
In simple terms: Some molecules can bind CCR2 at a different site inside the receptor and change how it responds.
Beyond the orthosteric site, CCR2 possesses an intracellular allosteric binding site that can be targeted by synthetic ligands. Fluorescent ligands have been developed that specifically target this intracellular allosteric site, enabling direct visualization of CCR2 binding events and providing tools to study receptor conformational states. This expands the pharmacological landscape of CCR2 chemokine receptor binding beyond classical chemokine orthosteric interactions.
Receptor activation and G-protein coupling
In simple terms: Once the ligand is bound, the receptor changes shape and switches on G proteins inside the cell.
Ligand binding stabilizes an active CCR2 conformation that couples to Gi-family G proteins, leading to inhibition of adenylyl cyclase and activation of downstream chemotactic signaling. This coupling is the functional consequence of CCR2 chemokine receptor binding and is required for monocyte directional migration. The CCL2-CCR2 axis is a validated target for atheroprotection, and interfering with this binding step reduces inflammatory cell recruitment.
Regulation of CCR2 binding availability
In simple terms: Cells can change how much CCR2 is on their surface, which controls how much ligand they can bind.
The availability of CCR2 for ligand binding is regulated at the level of receptor expression and trafficking. In metabolic-associated fatty liver disease, METTL14 downregulation drives S100A4-positive monocyte-derived macrophages via the MyD88/NF-kappaB pathway, a process linked to CCR2-positive monocyte biology. In obesity-induced cardiac dysfunction, Lysozyme 1 inflamed CCR2-positive macrophages promote disease, indicating that the inflammatory environment modulates CCR2-dependent recruitment. These findings show that CCR2 chemokine receptor binding is not static but is tuned by the cellular activation state.
Pathogen exploitation of CCR2 binding
In simple terms: Some viruses use CCR2 as a door to get inside cells.
CCR2 is a host entry receptor for severe fever with thrombocytopenia syndrome virus (SFTSV), meaning that the virus engages CCR2 to gain cellular entry. This demonstrates that the binding interface defined by GO:0031727 can be co-opted by non-chemokine ligands, with direct implications for antiviral strategies.
Key Genes Involved in GO:0031727 CCR2 chemokine receptor binding
The following genes and proteins are experimentally linked to CCR2 chemokine receptor binding and its downstream biology.
| Gene | Major Role | Research Relevance |
|---|---|---|
| CCR2 | Receptor that binds chemokine ligands | Core molecule of GO:0031727; target for KO and point-mutation studies |
| CCL2 | High-affinity ligand for CCR2 (MCP-1) | Principal binding partner; used in binding assays and KO models |
| CCL7 | Alternative CCR2 ligand | Modulates receptor binding specificity |
| CCL8 | Alternative CCR2 ligand | Contributes to CCR2-dependent chemotaxis |
| CCL13 | CCR2-binding chemokine | Studied in allergic and inflammatory contexts |
| CCL12 | Mouse CCR2 ligand | Used in murine inflammation models |
| LYZ1 | Lysozyme 1 in CCR2-positive macrophages | Linked to obesity-induced cardiac dysfunction |
| S100A4 | Marker of monocyte-derived macrophages | Associated with MAFLD progression via CCR2-positive cells |
| METTL14 | RNA methyltransferase regulating macrophage phenotype | Downregulation drives S100A4-positive macrophages |
| MYD88 | Adaptor in NF-kappaB signaling | Mediates inflammatory signaling in CCR2-positive macrophages |
| NFKB1 | Transcription factor downstream of MyD88 | Regulates inflammatory gene expression in CCR2 biology |
| PDCD1 | Immune checkpoint in T cells | Expanded T helper cells in rheumatoid arthritis interact with CCR2 axis |
| CXCL13 | Chemokine in lymphoid aggregates | Co-regulated with CCR2 in rheumatoid arthritis |
| IL21 | Cytokine from T helper cells | Associated with CCR2-positive T cell subsets |
| SFTSV Gn | Viral glycoprotein binding CCR2 | Mediates viral entry via CCR2 |
| IgG | Immunoglobulin in tumor microenvironment | Linked to glioblastoma stem cell maintenance with CCR2-positive infiltrate |
How Is CCR2 chemokine receptor binding Regulated?
CCR2 chemokine receptor binding is regulated at multiple levels. Receptor expression on monocytes and macrophages determines the number of available binding sites, and this expression is influenced by inflammatory stimuli and metabolic stress. In metabolic-associated fatty liver disease, METTL14 downregulation drives S100A4-positive monocyte-derived macrophages via the MyD88/NF-kappaB pathway, indirectly shaping the CCR2-positive compartment. In obesity-induced cardiac dysfunction, Lysozyme 1 inflamed CCR2-positive macrophages promote disease, indicating that the inflammatory milieu regulates CCR2-dependent recruitment. At the receptor level, intracellular allosteric sites provide additional regulatory nodes that can be engaged by synthetic ligands to modulate binding and signaling. Together, these mechanisms tune the intensity and duration of CCR2 chemokine receptor binding in vivo.
CCR2 chemokine receptor binding and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| CCR2 | Atherosclerosis | CCR2 knockout mouse and monocyte migration assays |
| CCL2 | Cardiovascular inflammation | CCL2 overexpression or knockout in endothelial cells |
| METTL14 | MAFLD progression | METTL14 knockdown in macrophages with CCR2 readout |
| LYZ1 | Obesity-induced cardiac dysfunction | Lysozyme 1 knockout in CCR2-positive macrophages |
| CCR2 | SFTSV viral entry | CCR2 knockout cell lines challenged with SFTSV |
Atherosclerosis and cardiovascular disease
The CCL2-CCR2 axis is a validated target for atheroprotection, and interrupting CCR2 chemokine receptor binding reduces monocyte recruitment into atherosclerotic lesions. This makes GO:0031727 a central molecular function in cardiovascular pathology and a focus for therapeutic development.
Metabolic and inflammatory liver disease
In metabolic-associated fatty liver disease (MAFLD), METTL14 downregulation drives S100A4-positive monocyte-derived macrophages via the MyD88/NF-kappaB pathway, a process dependent on CCR2-positive monocyte biology. Obesity-induced cardiac dysfunction is also promoted by Lysozyme 1 inflamed CCR2-positive macrophages, linking CCR2 binding to metabolic inflammation.
Viral infection
CCR2 is a host entry receptor for severe fever with thrombocytopenia syndrome virus (SFTSV), meaning the virus exploits the CCR2 binding interface to enter cells. This highlights GO:0031727 as a potential antiviral target and a model for pathogen-receptor interactions.
Autoimmune and tumor microenvironments
Pathologically expanded peripheral T helper cells drive B cells in rheumatoid arthritis, a process connected to CCR2-positive immune cell subsets. In glioblastoma, infiltrating plasma cells maintain glioblastoma stem cells through IgG-tumor binding, with CCR2-positive myeloid cells contributing to the microenvironment.
From CCR2 chemokine receptor binding-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does CCR2 binding drive monocyte recruitment? | CCR2 knockout mouse with CCL2 challenge |
| Which residues mediate ligand binding? | CCR2 point-mutation knock-in cell lines |
| Can allosteric ligands modulate CCR2 binding? | Fluorescent ligand binding assays in CCR2-expressing cells |
| Does CCR2 mediate SFTSV entry? | CCR2 knockout cells infected with SFTSV |
| How does METTL14 affect CCR2-positive macrophages? | METTL14 knockdown macrophages with CCR2 expression readout |
| Does Lysozyme 1 regulate CCR2 macrophage inflammation? | Lysozyme 1 knockout mouse with cardiac dysfunction model |
How to Study the CCR2 chemokine receptor binding Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Fluorescent ligand binding assay | Receptor occupancy and binding kinetics | Screening allosteric modulators of CCR2 |
| Radioligand binding | Affinity and competition at CCR2 | Characterizing chemokine-receptor interactions |
| CCR2 knockout mouse | In vivo monocyte recruitment | Atherosclerosis and inflammation models |
| Point-mutation knock-in | Residue-level binding determinants | Mapping the CCR2 ligand interface |
| Viral infection assay | SFTSV entry efficiency | Testing CCR2-dependent viral entry |
| Macrophage polarization assay | S100A4 and CCR2 expression | MAFLD and metabolic inflammation studies |
| Cardiac dysfunction model | Lysozyme 1 and CCR2 macrophage infiltration | Obesity-related heart disease |
| T helper cell expansion assay | Peripheral T helper subset frequency | Rheumatoid arthritis research |
Ligand binding assays
Direct measurement of CCR2 chemokine receptor binding is performed using radiolabeled or fluorescent chemokine ligands. Fluorescent ligands targeting the intracellular allosteric binding site of CCR2 enable real-time visualization of binding events and receptor occupancy in living cells. These assays are essential for determining affinity, kinetics, and competition between ligands.
Genetic perturbation and phenotyping
Knockout and knockdown of CCR2 or its ligands in cell lines and mouse models allows causal testing of GO:0031727 in monocyte recruitment and inflammation. For example, CCR2 knockout models demonstrate reduced monocyte infiltration in atherosclerosis, and METTL14 knockdown reveals effects on S100A4-positive macrophages.
Structural and computational analysis
Structural analysis of chemokine receptor-ligand interactions provides atomic-level insight into the CCR2 binding interface. Computational docking and molecular dynamics complement experimental structures to predict how mutations affect binding.
Viral entry and infection assays
Because CCR2 is a host entry receptor for SFTSV, viral infection assays in CCR2-expressing and CCR2-knockout cells can quantify the contribution of CCR2 binding to viral entry. These assays link the molecular function GO:0031727 to infectious disease outcomes.
How CRISPR Can Be Used to Study GO:0031727 CCR2 chemokine receptor binding
Knockout
CRISPR knockout of CCR2 or its ligands provides a clean genetic test of GO:0031727 function. CCR2 knockout cells and mice show reduced monocyte recruitment and attenuated inflammatory responses, validating the binding event as a causal node in disease models. Knockout of METTL14 in macrophages similarly reveals downstream effects on S100A4-positive monocyte-derived macrophages.
Point Mutation
Point mutations in CCR2 can be introduced to dissect the ligand binding interface. Structural analysis of chemokine receptor-ligand interactions identifies key residues, and point-mutation knock-in models allow testing of their contribution to binding affinity and signaling. Such models are valuable for separating binding from downstream activation.
Knock-in
Knock-in of tagged or fluorescent CCR2 allows direct visualization of receptor localization and binding in live cells. This approach complements fluorescent ligand studies that target the intracellular allosteric site of CCR2. Tagged knock-in models also enable tracking of receptor trafficking after ligand engagement.
Overexpression
Overexpression of CCR2 or CCL2 in cell lines amplifies the binding signal and facilitates biochemical and pharmacological assays. Overexpression systems are useful for screening small-molecule modulators of CCR2 chemokine receptor binding and for producing receptor protein for structural studies.
How EDITGENE Supports CCR2 chemokine receptor binding Research
Researchers studying CCR2 chemokine receptor binding-related genes often need to determine whether a candidate gene is causally involved in ligand recognition, receptor activation, or downstream inflammatory recruitment. Establishing causality requires precise genetic models that can isolate binding from signaling, and CRISPR-based approaches provide the necessary resolution. EDITGENE offers a suite of services tailored to CCR2 biology, from knockout to knock-in and library screening, enabling rigorous interrogation of GO:0031727 in relevant cell types.
Contact EDITGENE today to design your custom CRISPR model for CCR2 chemokine receptor binding research.
Frequently Asked Questions About CCR2 chemokine receptor binding
What is CCR2 chemokine receptor binding?
CCR2 chemokine receptor binding (GO:0031727) is the molecular function by which a chemokine ligand, such as CCL2, binds to the CCR2 receptor to initiate signaling.
What genes are involved in CCR2 chemokine receptor binding?
The core genes are CCR2 and its ligands CCL2, CCL7, CCL8, and CCL13, with downstream regulators including METTL14, MYD88, and NFKB1.
What is the GO ID for CCR2 chemokine receptor binding?
The Gene Ontology ID is GO:0031727, classified under molecular_function.
Which chemokine is the main ligand for CCR2?
CCL2, also known as monocyte chemoattractant protein 1 (MCP-1), is the principal high-affinity ligand for CCR2.
How is CCR2 chemokine receptor binding studied experimentally?
It is studied using fluorescent ligand binding assays, radioligand binding, knockout models, and structural analysis of chemokine-receptor interactions.
Why is CCR2 chemokine receptor binding important in disease?
It drives monocyte recruitment in atherosclerosis, metabolic inflammation, and serves as a viral entry receptor for SFTSV.
Can CCR2 be targeted therapeutically?
Yes, the CCL2-CCR2 axis is a validated target for atheroprotection, and allosteric ligands can modulate receptor binding.
What diseases are linked to CCR2 chemokine receptor binding?
Atherosclerosis, obesity-induced cardiac dysfunction, metabolic-associated fatty liver disease, rheumatoid arthritis, and SFTSV infection.
What cell types express CCR2?
CCR2 is expressed on monocytes, macrophages, and specific T helper cell subsets involved in inflammatory responses.
How does CRISPR help study CCR2 chemokine receptor binding?
CRISPR knockout, point mutation, knock-in, and overexpression models allow causal testing of CCR2 binding in inflammation and infection.
Conclusion
GO:0031727, CCR2 chemokine receptor binding, is a molecular function at the intersection of immunology, cardiovascular biology, and infectious disease. The binding of chemokines such as CCL2 to CCR2 initiates monocyte recruitment and inflammatory signaling that contributes to atherosclerosis, metabolic disease, and viral entry. Experimental tools including fluorescent ligands, knockout models, and structural analysis have clarified the binding interface and its regulation. Continued research using CRISPR-based models will refine our understanding of CCR2 chemokine receptor binding and support the development of targeted therapeutics.
References
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- 2. Gao J et al.. 2025. Infiltrating plasma cells maintain glioblastoma stem cells through IgG-Tumor binding.. Cancer Cell 43(1):122-143.e8 PMID: 39753140
- 3. Zhang L et al.. 2024. Lysozyme 1 Inflamed CCR2(+) Macrophages Promote Obesity-Induced Cardiac Dysfunction.. Circ Res 135(5):596-613 PMID: 39056179
- 4. Toy L et al.. 2022. Fluorescent Ligands Targeting the Intracellular Allosteric Binding Site of the Chemokine Receptor CCR2.. ACS Chem Biol 17(8):2142-2152 PMID: 35838163
- 5. Wang YF et al.. 2024. METTL14 downregulation drives S100A4(+) monocyte-derived macrophages via MyD88/NF-κB pathway to promote MAFLD progression.. Signal Transduct Target Ther 9(1):91 PMID: 38627387
- 6. Rao DA et al.. 2017. Pathologically expanded peripheral T helper cell subset drives B cells in rheumatoid arthritis.. Nature 542(7639):110-114 PMID: 28150777
- 7. Arimont M et al.. 2017. Structural Analysis of Chemokine Receptor-Ligand Interactions.. J Med Chem 60(12):4735-4779 PMID: 28165741
- 8. Georgakis MK et al.. 2022. Targeting the CCL2-CCR2 axis for atheroprotection.. Eur Heart J 43(19):1799-1808 PMID: 35567558
