GO:0070539 linoleic acid binding: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0070539 (linoleic acid binding) is a molecular function defined as binding to linoleic acid, an 18-carbon unsaturated fatty acid (9Z,12Z)-octadeca-9,12-dienoic acid.
• Key proteins that bind linoleic acid include FABP5, FABP7, and the SARS-CoV-2 spike glycoprotein, as shown by structural and functional studies [1,3,6].
• Linoleic acid binding can directly regulate signaling pathways such as mTORC1, linking dietary omega-6 fatty acids to cell growth and metabolism.
• In cancer, linoleic acid binding by FABP7 or LINC01116-mediated sequestration can influence tumor progression and immune evasion [6,7].
• Pathogens like Mycobacterium tuberculosis can exploit linoleic acid binding to modulate host immunity and promote survival.
• CRISPR-based models (knockout, point mutation, knock-in, overexpression) are essential to dissect the causal roles of linoleic acid-binding proteins in health and disease.
Description
Linoleic acid is a dietary omega-6 polyunsaturated fatty acid that serves as a precursor to various lipid mediators and is involved in numerous cellular processes. The Gene Ontology (GO) term GO:0070539, linoleic acid binding, describes the molecular function of selectively interacting with linoleic acid. This function is mediated by a diverse set of proteins, including fatty acid-binding proteins (FABPs), viral glycoproteins, and nuclear receptors, and it plays critical roles in metabolism, immunity, and disease [1,3,5,6]. Understanding linoleic acid binding is important because it can directly influence signaling pathways, such as mTORC1, and modulate cellular responses to dietary lipids. Moreover, pathogens and cancer cells can hijack linoleic acid binding to evade immune responses or promote growth, making it a target of therapeutic interest [2,7]. This article provides a comprehensive overview of the molecular mechanisms, key genes, disease associations, and research methods related to GO:0070539, with a focus on CRISPR-based approaches for functional studies.
linoleic acid binding At A Glance
| GO ID | GO:0070539 |
|---|---|
| GO term | linoleic acid binding |
| Ontology | molecular_function |
| Synonym | (none) |
| Major function | Binding to linoleic acid, an 18-carbon unsaturated fatty acid |
| Definition source | QuickGO |
| Related GO terms | fatty acid binding, long-chain fatty acid binding |
| Common gene families | FABP, PPAR, spike glycoprotein |
| Disease relevance | Cancer, infections, metabolic disorders |
What Is GO:0070539?
GO:0070539 (linoleic acid binding) is defined as the molecular function of binding to linoleic acid, the 18-carbon unsaturated fatty acid (9Z,12Z)-octadeca-9,12-dienoic acid. This term encompasses any protein or molecule that non-covalently interacts with linoleic acid, whether as a transporter, sensor, or structural component. It is a child of the broader GO term 'fatty acid binding' and is distinct from binding to other fatty acids such as oleic acid or arachidonic acid.
Why Is linoleic acid binding Important in Cell Biology?
Linoleic acid binding is important because it mediates the cellular response to a major dietary fatty acid and influences a wide range of physiological and pathological processes. For example, direct sensing of linoleic acid through FABP5-mTORC1 signaling links dietary omega-6 intake to cell growth and proliferation. In cancer, linoleic acid binding proteins such as FABP7 can modulate cell death pathways and affect tumor progression. Additionally, pathogens like Mycobacterium tuberculosis exploit linoleic acid binding to enhance regulatory T cell function and promote survival within macrophages. Therefore, understanding the molecular details of linoleic acid binding is crucial for developing therapeutic strategies against cancer, infectious diseases, and metabolic disorders.
• Linoleic acid binding regulates mTORC1 signaling, connecting diet to cell growth.
• It is involved in immune modulation by pathogens such as Mycobacterium tuberculosis.
• The SARS-CoV-2 spike protein binds linoleic acid, suggesting a potential antiviral target.
• FABP7-mediated linoleic acid binding can induce cell death in triple-negative breast cancer.
• Hepatocellular carcinoma cells can outcompete T cells for linoleic acid via LINC01116, promoting tumor progression.
• Conjugated linoleic acid regulates FABP expression through PPARα, affecting fat content.
• Linoleic acid binding to ovalbumin nanoparticles has applications in drug delivery.
• Virtual screening has identified drugs that bind the linoleic acid site on SARS-CoV-2 spike protein.
• It is a key molecular function for understanding lipid-mediated signaling and metabolism.
• CRISPR models enable precise dissection of linoleic acid binding in disease.
Molecular Mechanism of linoleic acid binding
Substrate recognition and binding pocket
In simple terms: Proteins have a specific pocket that fits linoleic acid like a lock and key.
Linoleic acid binding typically occurs through a hydrophobic binding pocket that accommodates the 18-carbon acyl chain. For example, the SARS-CoV-2 spike glycoprotein binds linoleic acid in a pocket that can also be targeted by approved drugs, as shown by cryo-EM and virtual screening [3,8]. Fatty acid-binding proteins (FABPs) such as FABP5 and FABP7 also possess a central cavity that binds linoleic acid with high affinity, facilitating its transport and signaling [1,6].
Conformational changes and signaling activation
In simple terms: When linoleic acid binds, it can flip a switch that turns on cellular signals.
Binding of linoleic acid can induce conformational changes that activate downstream signaling. For instance, direct sensing of dietary omega-6 linoleic acid through FABP5-mTORC1 signaling leads to mTORC1 activation, which promotes anabolic processes and cell growth. Similarly, linoleic acid binding to FABP7 modulates the production of 13-HODE, which can trigger cell death in triple-negative breast cancer cells.
Regulation by peroxisome proliferator-activated receptors
In simple terms: Some nuclear receptors respond to linoleic acid by changing gene expression.
Conjugated linoleic acid can regulate the expression of adipocyte fatty acid-binding protein via peroxisome proliferator-activated receptor α (PPARα) signaling, thereby influencing intramuscular fat content. This indicates that linoleic acid binding to PPARα or related factors can have transcriptional effects.
Pathogen exploitation of linoleic acid binding
In simple terms: Some bacteria use linoleic acid to calm the immune system and survive.
Mycobacterium tuberculosis-derived linoleic acid increases regulatory T cell function to promote bacterial survival within macrophages. This suggests that linoleic acid binding by host or bacterial proteins can modulate immune responses.
Competitive sequestration in the tumor microenvironment
In simple terms: Cancer cells can steal linoleic acid from immune cells to grow faster.
Hepatocellular carcinoma cells overexpress LINC01116, which outcompetes T cells for linoleic acid and accelerates tumor progression. This highlights the importance of linoleic acid availability and binding in immune evasion.
Key Genes Involved in GO:0070539 linoleic acid binding
The following genes and proteins are directly implicated in linoleic acid binding or its downstream effects, based on published literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| FABP5 | Binds linoleic acid and activates mTORC1 signaling | Links dietary omega-6 to cell growth |
| FABP7 | Binds linoleic acid and modulates 13-HODE production | Mediates cell death in triple-negative breast cancer |
| FABP4 | Adipocyte fatty acid-binding protein regulated by PPARα | Influences intramuscular fat content |
| PPARα | Nuclear receptor activated by conjugated linoleic acid | Regulates FABP expression and lipid metabolism |
| SPIKE | SARS-CoV-2 spike glycoprotein binds linoleic acid | Potential antiviral target [3,8] |
| LINC01116 | Long non-coding RNA that sequesters linoleic acid | Promotes tumor progression by outcompeting T cells |
| ALB | Ovalbumin nanoparticles bind linoleic acid | Drug delivery applications |
| MTB proteins | Mycobacterium tuberculosis components bind linoleic acid | Modulate regulatory T cell function |
| FABP3 | Heart-type fatty acid-binding protein | May bind linoleic acid (inferred from family) |
| FABP1 | Liver fatty acid-binding protein | May bind linoleic acid (inferred from family) |
| FABP2 | Intestinal fatty acid-binding protein | May bind linoleic acid (inferred from family) |
| CD36 | Fatty acid translocase | Facilitates linoleic acid uptake (inferred) |
| PPARγ | Nuclear receptor | May bind linoleic acid derivatives (inferred) |
| SLC27A1 | Fatty acid transport protein | Involved in linoleic acid uptake (inferred) |
| ACSL1 | Acyl-CoA synthetase | Activates linoleic acid to linoleoyl-CoA (inferred) |
| COX2 | Cyclooxygenase-2 | Metabolizes linoleic acid to prostaglandins (inferred) |
| LOX | Lipoxygenase | Metabolizes linoleic acid to HODEs (inferred) |
How Is linoleic acid binding Regulated?
Linoleic acid binding can be regulated at multiple levels. The expression of fatty acid-binding proteins such as FABP4 is regulated by PPARα signaling in response to conjugated linoleic acid. Additionally, the availability of linoleic acid itself can be modulated by dietary intake and cellular uptake mechanisms. In cancer, the long non-coding RNA LINC01116 can sequester linoleic acid, effectively reducing its availability to immune cells and thereby regulating anti-tumor immunity. Furthermore, direct binding of linoleic acid to FABP5 activates mTORC1, which in turn can feedback on lipid metabolism and cell growth. These examples illustrate that linoleic acid binding is dynamically controlled by transcriptional, post-transcriptional, and metabolic mechanisms.
linoleic acid binding and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| FABP7 | Triple-negative breast cancer | Knockout and overexpression in breast cancer cell lines |
| LINC01116 | Hepatocellular carcinoma | Knockdown and overexpression in liver cancer cells |
| SPIKE | COVID-19 | Point mutations in spike binding pocket |
| FABP4 | Metabolic disorders | Knockout mice and adipocyte cell models |
| MTB proteins | Tuberculosis | Macrophage infection models with gene knockouts |
Cancer
Linoleic acid binding proteins are implicated in multiple cancers. FABP7 mediates linoleic acid-induced cell death in triple-negative breast cancer cells by modulating 13-HODE, suggesting a tumor-suppressive role in this context. In contrast, hepatocellular carcinoma cells overexpress LINC01116, which outcompetes T cells for linoleic acid and accelerates tumor progression, indicating a pro-tumorigenic mechanism. These findings highlight the context-dependent roles of linoleic acid binding in cancer.
Infectious diseases
Mycobacterium tuberculosis-derived linoleic acid increases regulatory T cell function to promote bacterial survival within macrophages, suggesting that linoleic acid binding can be exploited by pathogens to evade host immunity. Additionally, the SARS-CoV-2 spike glycoprotein binds linoleic acid, and this interaction can be targeted by approved drugs, offering a potential antiviral strategy [3,8].
Metabolic disorders
Conjugated linoleic acid regulates adipocyte fatty acid-binding protein expression via PPARα signaling and increases intramuscular fat content, linking linoleic acid binding to lipid metabolism and potentially to obesity and metabolic syndrome.
From linoleic acid binding-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does FABP5 mediate linoleic acid-induced mTORC1 activation? | FABP5 knockout cell lines |
| What is the role of FABP7 in breast cancer cell death? | FABP7 overexpression and knockout in TNBC cells |
| Can point mutations in spike protein abolish linoleic acid binding? | Point-mutant spike knock-in cells |
| How does LINC01116 affect T cell competition for linoleic acid? | LINC01116 knockout in hepatocellular carcinoma cells |
| Does PPARα regulate FABP4 expression in response to linoleic acid? | PPARα knockout adipocytes |
| Can linoleic acid binding be targeted for antiviral therapy? | Tagged knock-in of spike protein for drug screening |
How to Study the linoleic acid binding Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Isothermal titration calorimetry | Binding affinity and thermodynamics | Characterize purified proteins |
| Cryo-EM | 3D structure of protein-ligand complex | Determine binding pocket |
| CRISPR knockout screen | Genes required for linoleic acid binding | Identify novel regulators |
| RNA-seq | Transcriptional changes upon linoleic acid treatment | Pathway analysis |
| Lipidomics | Levels of linoleic acid and metabolites | Metabolic profiling |
| Fluorescence polarization | Binding affinity in solution | High-throughput screening |
| Molecular dynamics simulation | Binding stability and interactions | Virtual screening |
Lipid binding assays
Direct measurement of linoleic acid binding can be performed using isothermal titration calorimetry, fluorescence polarization, or radioligand binding assays. These methods quantify binding affinity and stoichiometry, as demonstrated for ovalbumin nanoparticles and FABP7.
Structural biology
Cryo-EM and X-ray crystallography can reveal the atomic details of linoleic acid binding pockets. For example, cryo-EM revealed the binding of linoleic acid to SARS-CoV-2 spike glycoprotein, providing a basis for antiviral design.
Functional genomics
CRISPR knockout screens and RNA-seq can identify genes required for linoleic acid binding or downstream signaling. Overexpression and knockdown studies can validate candidate genes, as shown for FABP5 in mTORC1 signaling and LINC01116 in tumor progression.
Metabolomics and lipidomics
Mass spectrometry-based lipidomics can quantify linoleic acid and its metabolites, such as 13-HODE, to assess the impact of binding on cellular metabolism.
How CRISPR Can Be Used to Study GO:0070539 linoleic acid binding
Knockout
CRISPR knockout of genes encoding linoleic acid-binding proteins, such as FABP5 or FABP7, can abolish binding and reveal downstream effects. For example, FABP5 knockout would test its role in mTORC1 activation by linoleic acid. Knockout of LINC01116 could restore T cell access to linoleic acid in tumors.
Point Mutation
Introducing point mutations in the binding pocket of proteins like the SARS-CoV-2 spike glycoprotein can disrupt linoleic acid binding and assess its functional importance [3,8]. This approach can also be used to study FABP7 mutants that fail to bind linoleic acid.
Knock-in
Knock-in of tagged versions of linoleic acid-binding proteins (e.g., GFP-FABP5) allows for live-cell imaging and pull-down assays to study localization and interactions. Knock-in of disease-associated mutations can model human conditions.
Overexpression
Overexpression of linoleic acid-binding proteins, such as FABP7 or LINC01116, can mimic disease states and test therapeutic interventions. For instance, overexpression of LINC01116 in hepatocellular carcinoma cells accelerates tumor progression.
How EDITGENE Supports linoleic acid binding Research
Researchers studying linoleic acid binding-related genes often need to determine whether a candidate gene is causally involved in a specific phenotype, such as cancer cell death or immune evasion. CRISPR-based models provide a robust way to manipulate these genes and dissect their functions.
Contact EDITGENE today to design your custom CRISPR model for linoleic acid binding research.
Frequently Asked Questions About linoleic acid binding
What is linoleic acid binding?
Linoleic acid binding is a molecular function (GO:0070539) where a protein or molecule selectively interacts with linoleic acid, an 18-carbon unsaturated fatty acid.
What genes are involved in linoleic acid binding?
Key genes include FABP5, FABP7, FABP4, PPARα, and the SARS-CoV-2 spike gene, among others [1,3,5,6].
How does linoleic acid binding affect cancer?
In cancer, linoleic acid binding can either promote cell death, as seen with FABP7 in breast cancer, or support tumor progression, as with LINC01116 in liver cancer.
What is the role of FABP5 in linoleic acid binding?
FABP5 binds linoleic acid and activates mTORC1 signaling, linking dietary omega-6 to cell growth.
Can viruses bind linoleic acid?
Yes, the SARS-CoV-2 spike protein binds linoleic acid, and this interaction can be targeted by drugs [3,8].
How is linoleic acid binding studied?
Methods include isothermal titration calorimetry, cryo-EM, CRISPR screens, and lipidomics [3,4,6].
What diseases are associated with linoleic acid binding?
Diseases include cancer, tuberculosis, COVID-19, and metabolic disorders [2,3,5,6,7].
What are the synonyms for GO:0070539?
There are no synonyms listed for this term.
Which ontology does linoleic acid binding belong to?
It belongs to the molecular_function ontology.
How can CRISPR help study linoleic acid binding?
CRISPR knockout, point mutation, knock-in, and overexpression models allow precise manipulation of genes to test their roles in linoleic acid binding and disease.
Conclusion
GO:0070539 (linoleic acid binding) represents a critical molecular function that mediates the cellular response to a major dietary fatty acid. Through proteins such as FABP5, FABP7, and the SARS-CoV-2 spike glycoprotein, linoleic acid binding influences signaling pathways, immune responses, and disease progression. Understanding these interactions offers opportunities for therapeutic intervention in cancer, infectious diseases, and metabolic disorders. CRISPR-based models are indispensable for dissecting the causal roles of linoleic acid-binding proteins, and EDITGENE provides comprehensive services to support such research.
References
- 1. Koundouros N et al.. 2025. Direct sensing of dietary ω-6 linoleic acid through FABP5-mTORC1 signaling.. Science 387(6739):eadm9805 PMID: 40080571
- 2. Cheng H et al.. 2025. Mycobacterium tuberculosis-derived linoleic acid increases regulatory T cell function to promote bacterial survival within macrophages.. Nat Microbiol 10(11):2949-2965 PMID: 41073667
- 3. Toelzer C et al.. 2023. Cryo-EM reveals binding of linoleic acid to SARS-CoV-2 spike glycoprotein, suggesting an antiviral treatment strategy.. Acta Crystallogr D Struct Biol 79(Pt 2):111-121 PMID: 36762857
- 4. Sponton OE et al.. 2015. Linoleic acid binding properties of ovalbumin nanoparticles.. Colloids Surf B Biointerfaces 128:219-226 PMID: 25701117
- 5. Chen J et al.. 2022. Conjugated linoleic acid regulates adipocyte fatty acid binding protein expression via peroxisome proliferator-activated receptor α signaling pathway and increases intramuscular fat content.. Front Nutr 9:1029864 PMID: 36523338
- 6. Kwong SC et al.. 2020. Fatty acid binding protein 7 mediates linoleic acid-induced cell death in triple negative breast cancer cells by modulating 13-HODE.. Biochimie 179:23-31 PMID: 32931863
- 7. Ma K et al.. 2024. Hepatocellular Carcinoma LINC01116 Outcompetes T Cells for Linoleic Acid and Accelerates Tumor Progression.. Adv Sci (Weinh) 11(21):e2400676 PMID: 38460179
- 8. Prajapat M et al.. 2022. Virtual screening and molecular dynamics simulation study of approved drugs as a binder to the linoleic acid binding site on spike protein of SARS-CoV-2 and double mutant (E484Q and L452R).. Indian J Pharmacol 54(6):431-442 PMID: 36722555
