GO:0071791 chemokine (C-C motif) ligand 5 binding: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0071791 (chemokine (C-C motif) ligand 5 binding) is a molecular function defined as binding to chemokine (C-C motif) ligand 5 (CCL5/RANTES).
• CCL5 is a secreted chemokine that signals through CCR5 and other receptors, and its binding interactions are central to immune cell recruitment and cancer progression.
• CCL5 binding is implicated in osteosarcoma, breast cancer, atherosclerosis, and metabolic regulation, making it a candidate biomarker and immunotherapy target [1,5,6,7,8].
• Key genes and proteins involved include CCL5, CCR5, GPR75, HIF-1α, and cancer-associated fibroblast markers [4,5,6].
• Experimental models for studying CCL5 binding include knockout mice, point-mutation knock-in, and overexpression cell lines [1,4,8].
• CRISPR-based knockout, knock-in, and overexpression models enable causal interrogation of CCL5 binding in disease contexts [1,5,8].
Description
Chemokine (C-C motif) ligand 5 binding (GO:0071791) is a molecular function that describes the physical interaction between a protein and the chemokine CCL5, also known as RANTES (Regulated upon Activation, Normal T-cell Expressed, and Secreted). CCL5 is a secreted chemokine that plays a critical role in immune cell trafficking and inflammation, and its binding to receptors such as CCR5 initiates signaling cascades that influence cell migration, proliferation, and survival. Understanding this binding event is essential for researchers studying cancer biology, immune regulation, and inflammatory diseases [1,3]. The interaction of CCL5 with its binding partners has been implicated in the progression of osteosarcoma, where CCL5 serves as a potential biomarker and immunotherapy target. In breast cancer, CCL5 binding contributes to premetastatic niche formation and macrophage crosstalk, highlighting its importance in tumor microenvironment remodeling [5,8]. Additionally, CCL5 acts as a negative regulator of GPR75, a receptor involved in 20-HETE signaling, demonstrating the breadth of its functional interactions. This article synthesizes current knowledge on the molecular mechanism, key genes, disease relevance, and research methodologies associated with GO:0071791, providing a resource for investigators aiming to interrogate this binding event using CRISPR-based models and other experimental approaches.
chemokine (C-C motif) ligand 5 binding At A Glance
| GO ID | GO:0071791 |
|---|---|
| GO term | chemokine (C-C motif) ligand 5 binding |
| Ontology | molecular_function |
| Synonym | CCL5 binding; RANTES binding; Regulated upon Activation, Normal T-cell Expressed, and Secreted binding |
| Major function | Binding to the chemokine CCL5, mediating interactions that influence immune cell recruitment, cancer progression, and inflammatory responses |
| Definition source | QuickGO |
| Related chemokine | CCL5 (RANTES) |
| Common binding partners | CCR5, GPR75, and other chemokine receptors or matrix components |
| Disease associations | Osteosarcoma, breast cancer, atherosclerosis, metabolic disorders |
What Is GO:0071791?
GO:0071791, chemokine (C-C motif) ligand 5 binding, is defined as the selective and non-covalent interaction of a molecule with CCL5, a small secreted cytokine belonging to the CC chemokine family. This binding event is a molecular function that can occur on the cell surface, in the extracellular matrix, or in solution, and it typically precedes or modulates downstream signaling through chemokine receptors such as CCR5. The term encompasses interactions with CCL5 in its monomeric, dimeric, or higher-order forms, and it is distinct from receptor activation or signal transduction, which are separate ontological functions.
Why Is chemokine (C-C motif) ligand 5 binding Important in Cell Biology?
GO:0071791 is important because CCL5 binding is a pivotal event in immune cell recruitment and tumor microenvironment communication, and its dysregulation is linked to cancer progression, metastasis, and inflammatory diseases [1,3,5]. In osteosarcoma, CCL5 binding contributes to tumor growth and immune evasion, positioning it as a therapeutic target. In breast cancer, CCL5 binding facilitates premetastatic niche formation and M2 macrophage crosstalk, driving disease progression [5,8]. Furthermore, CCL5 acts as a negative regulator of GPR75, influencing vascular and metabolic signaling. Studying this binding event can reveal mechanisms of disease and guide the development of targeted therapies, including monoclonal antibodies and small molecule inhibitors [3,7].
• CCL5 binding is a key step in immune cell chemotaxis and inflammation.
• It is implicated in osteosarcoma progression and serves as a potential immunotherapy target.
• CCL5 binding promotes premetastatic niche formation in breast cancer.
• It mediates crosstalk between M2 macrophages and breast cancer cells, enhancing tumor progression.
• CCL5 acts as a negative regulator of GPR75, affecting 20-HETE signaling.
• Disruption of CCL5 binding may improve atherosclerosis by inhibiting ceramide generation.
• CCL5 binding is a candidate biomarker for cancer diagnosis and prognosis [1,3].
• Targeting CCL5 binding with CBD shows antitumor effects in osteosarcoma.
• Understanding CCL5 binding aids in designing CCR5 antagonists and other therapeutics.
• CRISPR models enable functional dissection of CCL5 binding in disease [1,5,8].
Molecular Mechanism of chemokine (C-C motif) ligand 5 binding
CCL5 Structure and Binding Interface
In simple terms: CCL5 is a small protein that binds to receptors on cells, and its shape determines how it interacts.
CCL5 is a 68-amino-acid chemokine that adopts a typical CC chemokine fold, characterized by a disordered N-terminus and a structured core with two disulfide bonds. The binding interface of CCL5 with its receptors, such as CCR5, involves the N-terminal region and the loop between the second and third beta-strands. Structural studies have revealed that CCL5 can form dimers and higher-order oligomers, which may influence its binding affinity and receptor selectivity. The interaction with GPR75, a receptor for 20-HETE, identifies CCL5 as a negative regulator, suggesting a distinct binding mode compared to CCR5.
Receptor Interaction and Signaling
In simple terms: When CCL5 binds to a receptor, it triggers signals inside the cell that can change cell behavior.
CCL5 binding to CCR5, a G protein-coupled receptor, activates downstream signaling pathways including calcium flux, MAPK, and PI3K/Akt, leading to cell migration and survival. In cancer cells, CCL5 binding promotes proliferation and invasion through the activation of NF-κB and other transcription factors [1,7]. The binding of CCL5 to GPR75 negatively regulates 20-HETE-induced signaling, which affects vascular tone and metabolic pathways. Additionally, CCL5 binding to CCR5 on macrophages induces M2 polarization, which in turn secretes more CCL5, creating a feedback loop that amplifies tumor progression.
Regulation of CCL5 Binding by the Tumor Microenvironment
In simple terms: The environment around a tumor can change how much CCL5 is present and how it binds to cells.
Cancer-associated fibroblasts (CAFs) in the tumor microenvironment can secrete CCL5, which binds to receptors on cancer cells and endothelial cells, promoting angiogenesis and vascular permeability. Hypoxia-inducible factor 1-alpha (HIF-1α) regulates CCL5 expression in adipocytes, and disruption of this pathway affects atherosclerosis by inhibiting ceramide generation. The lncRNA SNHG5 mediates CCL5 secretion from CAFs, enhancing premetastatic niche formation in breast cancer. These regulatory mechanisms underscore the context-dependent nature of CCL5 binding and its impact on disease progression.
Therapeutic Targeting of CCL5 Binding
In simple terms: Drugs that block CCL5 from binding to its receptors could treat cancer and other diseases.
Cannabidiol (CBD) has been shown to exert antitumor effects in osteosarcoma by targeting the TNF-α/NF-κB/CCL5 signaling axis, reducing CCL5 binding and downstream signaling. Monoclonal antibodies against CCL5 or its receptors, such as CCR5 antagonists (e.g., maraviroc), are being explored to disrupt binding and inhibit tumor growth. In atherosclerosis, inhibiting CCL5 binding through HIF-1α disruption reduces ceramide generation and plaque formation. These therapeutic strategies highlight the clinical potential of modulating GO:0071791.
Key Genes Involved in GO:0071791 chemokine (C-C motif) ligand 5 binding
The following genes and proteins are central to chemokine (C-C motif) ligand 5 binding and its downstream effects.
| Gene | Major Role | Research Relevance |
|---|---|---|
| CCL5 | Ligand that binds to receptors; secreted chemokine | Biomarker and immunotherapy target in osteosarcoma and breast cancer [1,5] |
| CCR5 | Primary receptor for CCL5; mediates signaling | Target for HIV entry and cancer therapy |
| GPR75 | Receptor for 20-HETE; negatively regulated by CCL5 binding | Involved in vascular and metabolic signaling |
| HIF-1α | Transcription factor regulating CCL5 expression in adipocytes | Linked to atherosclerosis and ceramide generation |
| SNHG5 | Long non-coding RNA mediating CCL5 secretion from CAFs | Promotes premetastatic niche in breast cancer |
| TNF-α | Cytokine that induces CCL5 expression via NF-κB | Targeted by CBD in osteosarcoma |
| NF-κB | Transcription factor downstream of CCL5 binding | Drives inflammatory and oncogenic gene expression |
| MRO | Protein involved in M2 macrophage crosstalk with CCL5 | Feedback loop in breast cancer progression |
| HNRNPU | RNA-binding protein in MRO/HNRNPU/CCL5 loop | Amplifies M2 macrophage and cancer cell crosstalk |
| BDNF | Neurotrophic factor; muscle-generated, maintains mitochondrial quality | Potential indirect link to CCL5 binding in muscle |
| CCR1 | Alternative receptor for CCL5 | Mediates monocyte recruitment |
| CCR3 | Alternative receptor for CCL5 | Eosinophil chemotaxis |
| CD44 | Cell surface glycoprotein; can bind CCL5 | Involved in immune cell adhesion |
| Glycosaminoglycans | Extracellular matrix components that bind CCL5 | Modulate chemokine gradient formation |
| DARC | Duffy antigen receptor for chemokines; binds CCL5 | Acts as a decoy receptor |
| CCL5 variants | Genetic polymorphisms affecting binding affinity | Associated with disease susceptibility |
| CAF markers (FAP, α-SMA) | Cancer-associated fibroblasts secreting CCL5 | Promote angiogenesis and vascular permeability |
How Is chemokine (C-C motif) ligand 5 binding Regulated?
CCL5 binding is regulated at multiple levels, including expression of CCL5 and its receptors, post-translational modifications, and the presence of decoy receptors. HIF-1α regulates CCL5 expression in adipocytes under hypoxic conditions, and disruption of this pathway affects atherosclerosis. The lncRNA SNHG5 mediates CCL5 secretion from cancer-associated fibroblasts, enhancing binding to endothelial cells. In breast cancer, a feedback loop involving MRO, HNRNPU, and CCL5 amplifies M2 macrophage crosstalk, increasing CCL5 binding and tumor progression. Additionally, CCL5 binding to GPR75 negatively regulates 20-HETE signaling, providing a layer of metabolic control.
chemokine (C-C motif) ligand 5 binding and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| CCL5 | Osteosarcoma | CCL5 knockout osteosarcoma cell lines and xenograft mice |
| CCR5 | Breast cancer metastasis | CCR5 knockout or point-mutation knock-in in breast cancer cells [3,5] |
| GPR75 | Atherosclerosis | GPR75 knockout mice and CCL5 overexpression models [4,6] |
| HIF-1α | Metabolic disease | Adipocyte-specific HIF-1α knockout mice |
| SNHG5 | Breast cancer premetastatic niche | SNHG5 knockout CAFs and co-culture with cancer cells |
CCL5 Binding in Osteosarcoma
Osteosarcoma is a primary bone malignancy with high metastatic potential. CCL5 binding to CCR5 on osteosarcoma cells activates NF-κB signaling, promoting proliferation and invasion. Elevated CCL5 levels correlate with poor prognosis, and targeting CCL5 binding using cannabidiol (CBD) reduces tumor growth in preclinical models. Thus, CCL5 binding is a promising therapeutic target and biomarker for osteosarcoma [1,7].
CCL5 Binding in Breast Cancer Metastasis
In breast cancer, cancer-associated fibroblasts secrete CCL5, which binds to receptors on cancer cells and endothelial cells, facilitating premetastatic niche formation and vascular permeability. A feedback loop involving MRO, HNRNPU, and CCL5 amplifies M2 macrophage and cancer cell crosstalk, driving progression. These findings suggest that disrupting CCL5 binding could inhibit metastasis and improve patient outcomes [5,8].
CCL5 Binding in Atherosclerosis and Metabolic Disease
Disruption of adipocyte HIF-1α improves atherosclerosis by inhibiting ceramide generation, a process linked to CCL5 binding. CCL5 acts as a negative regulator of GPR75, affecting 20-HETE signaling, which influences vascular tone and metabolic homeostasis. Therefore, CCL5 binding is implicated in cardiovascular and metabolic diseases, offering potential targets for intervention [4,6].
From chemokine (C-C motif) ligand 5 binding-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does CCL5 binding promote tumor growth? | CCL5 knockout cancer cell lines and mouse xenografts |
| What is the binding affinity of CCL5 to CCR5? | Point-mutation knock-in of CCR5 binding residues |
| Can CCL5 binding be blocked therapeutically? | Knock-in of tagged CCL5 for imaging and drug screening |
| How does CCL5 binding affect macrophage polarization? | Overexpression of CCL5 in macrophages and co-culture |
| Does HIF-1α regulate CCL5 binding in adipocytes? | Adipocyte-specific HIF-1α knockout mice |
| What is the role of SNHG5 in CCL5 secretion? | SNHG5 knockout CAFs and conditioned media transfer |
How to Study the chemokine (C-C motif) ligand 5 binding Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Surface plasmon resonance (SPR) | Binding affinity and kinetics | Measuring CCL5-CCR5 interaction |
| ELISA | Quantification of CCL5 binding | Detecting CCL5 in serum or conditioned media |
| Flow cytometry | Cell surface binding of CCL5 | Analyzing receptor expression and binding |
| CRISPR knockout screening | Genes regulating CCL5 binding | Identifying modifiers of metastasis |
| RNA-seq | Transcriptional changes | Downstream effects of CCL5 binding |
| Mass spectrometry | Protein-protein interactions | Identifying novel CCL5 binding partners |
| Intravital microscopy | Real-time binding in vivo | Visualizing CCL5 binding in tumors |
| Xenograft models | Tumor growth and metastasis | Testing CCL5-targeted therapies [1,7] |
Binding Assays for CCL5 Interactions
Surface plasmon resonance (SPR) and isothermal titration calorimetry (ITC) can measure the binding affinity and kinetics of CCL5 to its receptors or matrix components. Enzyme-linked immunosorbent assay (ELISA) and flow cytometry are used to detect CCL5 binding to cell surfaces. These methods are essential for quantifying GO:0071791 activity in vitro.
CRISPR Screening to Identify CCL5 Binding Regulators
Genome-wide CRISPR knockout screens can identify genes that regulate CCL5 binding and downstream signaling. For example, screening in breast cancer cells treated with CCL5 can reveal modifiers of metastasis. Bioinformatics analysis of screen hits can uncover pathways enriched in CCL5 binding.
Transcriptomics and Proteomics
RNA sequencing (RNA-seq) of cells stimulated with CCL5 can reveal transcriptional changes downstream of binding. Proteomic profiling of CCL5-bound complexes using mass spectrometry can identify novel binding partners. These approaches provide a systems-level view of GO:0071791.
In Vivo Models for CCL5 Binding
Mouse models with CCL5 or receptor knockouts are used to study the role of CCL5 binding in tumor growth and metastasis [1,6]. Xenograft and syngeneic models allow assessment of therapeutic interventions targeting CCL5 binding. Imaging techniques such as intravital microscopy can visualize CCL5 binding in real time.
How CRISPR Can Be Used to Study GO:0071791 chemokine (C-C motif) ligand 5 binding
Knockout
CRISPR knockout of CCL5 or its receptors (e.g., CCR5) in cancer cell lines abolishes CCL5 binding and downstream signaling, enabling functional studies of GO:0071791 [1,3]. Knockout mice for CCL5 or CCR5 are used to assess the role of binding in tumor progression and atherosclerosis.
Point Mutation
Point mutations in the CCL5 binding interface of CCR5 or GPR75 can be introduced using CRISPR base editing or homology-directed repair to dissect specific residues required for binding [3,4]. Such models help distinguish binding from signaling.
Knock-in
Knock-in of tagged CCL5 (e.g., HA or GFP) allows visualization and pull-down of CCL5-binding complexes. Knock-in of disease-associated CCL5 variants can model altered binding affinity.
Overexpression
Overexpression of CCL5 in cancer cells or fibroblasts using CRISPR activation (CRISPRa) or lentiviral vectors increases CCL5 binding and promotes tumor progression [5,8]. Overexpression models are useful for studying gain-of-function effects.
How EDITGENE Supports chemokine (C-C motif) ligand 5 binding Research
Researchers studying chemokine (C-C motif) ligand 5 binding-related genes often need to determine whether a candidate gene is causally involved in binding, signaling, or disease progression. EDITGENE provides comprehensive CRISPR-based services to generate knockout, point-mutation, knock-in, and overexpression cell models, as well as library screening and bioinformatics support, enabling rigorous interrogation of GO:0071791 in any biological context.
Contact EDITGENE today to design your custom CRISPR model for chemokine (C-C motif) ligand 5 binding research.
Frequently Asked Questions About chemokine (C-C motif) ligand 5 binding
What is chemokine (C-C motif) ligand 5 binding?
Chemokine (C-C motif) ligand 5 binding (GO:0071791) is a molecular function describing the interaction of a protein with CCL5, a chemokine involved in immune cell recruitment and cancer progression.
What genes are involved in chemokine (C-C motif) ligand 5 binding?
Key genes include CCL5, CCR5, GPR75, HIF-1α, and SNHG5, among others [3,4,5,6].
How is CCL5 binding studied?
It is studied using binding assays like SPR and ELISA, CRISPR screens, RNA-seq, and in vivo models [1,3,5].
What diseases are associated with CCL5 binding?
CCL5 binding is linked to osteosarcoma, breast cancer, atherosclerosis, and metabolic disorders [1,5,6].
What is the role of CCL5 binding in cancer?
CCL5 binding promotes tumor growth, metastasis, and immune evasion, making it a therapeutic target [1,3,5].
Can CRISPR be used to study CCL5 binding?
Yes, CRISPR knockout, knock-in, and overexpression models enable functional dissection of CCL5 binding [1,5,8].
What is the difference between CCL5 and RANTES?
CCL5 and RANTES refer to the same chemokine; RANTES is an acronym for Regulated upon Activation, Normal T-cell Expressed, and Secreted.
How does CCL5 binding affect macrophages?
CCL5 binding induces M2 macrophage polarization, which promotes tumor progression through a feedback loop.
What are the therapeutic strategies targeting CCL5 binding?
Strategies include monoclonal antibodies, CCR5 antagonists, and natural compounds like cannabidiol [3,7].
What model systems are available for CCL5 binding research?
Knockout mice, point-mutation cell lines, and overexpression models are commonly used [1,4,6].
Conclusion
GO:0071791, chemokine (C-C motif) ligand 5 binding, is a critical molecular function with broad implications in cancer, cardiovascular disease, and immune regulation. Understanding the mechanisms, key genes, and regulatory networks of CCL5 binding provides a foundation for developing targeted therapies. CRISPR-based models and advanced screening technologies offer powerful tools to interrogate this binding event and translate findings into clinical applications.
References
- 1. Zheng H et al.. 2024. C-C Motif Chemokine Ligand 5 (CCL5): A Potential Biomarker and Immunotherapy Target for Osteosarcoma.. Curr Cancer Drug Targets 24(3):308-318 PMID: 37581517
- 2. Ahuja P et al.. 2022. Muscle-generated BDNF (brain derived neurotrophic factor) maintains mitochondrial quality control in female mice.. Autophagy 18(6):1367-1384 PMID: 34689722
- 3. Ghasemi K. 2025. C-C motif glycoprotein ligand 5 (CCL5) and its GPCR CCR5: Macromolecular game-changers in cancer biology.. Int J Biol Macromol 329(Pt 1):147737 PMID: 40976299
- 4. Pascale JV et al.. 2021. Uncovering the signalling, structure and function of the 20-HETE-GPR75 pairing: Identifying the chemokine CCL5 as a negative regulator of GPR75.. Br J Pharmacol 178(18):3813-3828 PMID: 33974269
- 5. Zeng H et al.. 2022. Cancer-associated fibroblasts facilitate premetastatic niche formation through lncRNA SNHG5-mediated angiogenesis and vascular permeability in breast cancer.. Theranostics 12(17):7351-7370 PMID: 36438499
- 6. Wang P et al.. 2022. Disruption of adipocyte HIF-1α improves atherosclerosis through the inhibition of ceramide generation.. Acta Pharm Sin B 12(4):1899-1912 PMID: 35847503
- 7. Yang F et al.. 2025. Antitumor effects of cannabidiol (CBD) on osteosarcoma by targeting TNF-α/NF-κB/CCL5 signaling axis.. Phytomedicine 145:157066 PMID: 40680332
- 8. Zeng Z et al.. 2025. MRO/HNRNPU/CCL5 feedback loop amplifies M2 macrophage and breast cancer cell crosstalk to drive progression.. J Transl Med 23(1):920 PMID: 40817243
