GO:0070538 oleic acid binding: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0070538 (oleic acid binding) is a molecular_function term describing binding to oleic acid, the 18-carbon monounsaturated fatty acid (9Z)-octadec-9-enoic acid.
• Oleic acid binding proteins include intracellular lipid chaperones such as FABP4 and FABP5, membrane receptors, serum albumin, and odorant-binding proteins.
• Oleic acid binding regulates lipid accumulation, apoptosis, mitochondrial function, and metabolic signaling in hepatocytes and other cell types.
• Dysregulated oleic acid binding is linked to colorectal cancer progression, metabolic syndrome-associated endometrial cancer, and cardiac mitochondrial dysfunction.
• Experimental approaches to study oleic acid binding include isothermal titration calorimetry, fluorescence spectroscopy, and lipidomics.
• CRISPR-based knockout, point-mutation, knock-in, and overexpression models enable causal testing of oleic acid binding proteins in disease biology.
Description
Oleic acid binding (GO:0070538) is a molecular function defined as binding to oleic acid, the 18-carbon monounsaturated fatty acid (9Z)-octadec-9-enoic acid. This term captures the physical interaction between a protein or macromolecule and oleic acid, a central fatty acid in human metabolism and disease. Oleic acid is the most abundant monounsaturated fatty acid in many tissues and serves both as a metabolic substrate and as a signaling molecule. Proteins that bind oleic acid participate in lipid transport, metabolic regulation, and cellular stress responses. The importance of oleic acid binding extends across physiology and pathology. In hepatocytes, oleic acid binding influences lipid accumulation and apoptosis, with differential effects compared to saturated fatty acids such as palmitic acid. In the heart, oleic acid binding to adrenaline ameliorates adrenaline-induced mitochondrial dysfunction, revealing a direct molecular interaction with signaling molecules. In cancer, oleic acid-mediated metabolic reprogramming promotes polyamine accumulation in endometrial cancer under metabolic syndrome conditions, and plasma metabolomics identifies oleic acid as a functional metabolite in adenoma-colorectal cancer progression. For researchers, GO:0070538 provides a precise annotation for proteins that directly interact with oleic acid. Understanding these interactions requires integrating structural biology, lipid biochemistry, and functional genomics. This article reviews the definition, mechanisms, key genes, disease relevance, and research methods for studying oleic acid binding, with a focus on CRISPR-based models for causal validation.
oleic acid binding At A Glance
| GO ID | GO:0070538 |
|---|---|
| GO term | oleic acid binding |
| Ontology | molecular_function |
| Synonym | (none) |
| Definition | Binding to oleic acid, the 18-carbon monounsaturated fatty acid (9Z)-octadec-9-enoic acid. |
| Major function | Non-covalent interaction with oleic acid, enabling lipid sensing, transport, and metabolic regulation. |
| Representative proteins | FABP4, FABP5, serum albumin, odorant-binding proteins, and other lipid-binding proteins. |
| Disease relevance | Colorectal cancer, endometrial cancer, metabolic syndrome, cardiac mitochondrial dysfunction. |
| Research methods | Isothermal titration calorimetry, fluorescence spectroscopy, lipidomics, and CRISPR screens. |
What Is GO:0070538?
GO:0070538 (oleic acid binding) is a Gene Ontology molecular_function term defined as binding to oleic acid, the 18-carbon monounsaturated fatty acid (9Z)-octadec-9-enoic acid. In practical terms, it describes the selective, non-covalent interaction between a protein or macromolecular complex and oleic acid. This binding can be reversible and may involve hydrophobic pockets, lipid-binding domains, or electrostatic interactions. The term does not imply catalysis or transport per se, but rather the physical association with oleic acid as a ligand.
Why Is oleic acid binding Important in Cell Biology?
Oleic acid binding is important because oleic acid is a central monounsaturated fatty acid in human metabolism, and its interactions with proteins influence lipid storage, apoptosis, mitochondrial function, and cancer progression. The GO term GO:0070538 provides a standardized annotation for these interactions, enabling researchers to identify and compare oleic acid-binding proteins across species and experimental systems. Dysregulation of oleic acid binding has been implicated in metabolic syndrome, colorectal cancer, and endometrial cancer, making it a target for mechanistic studies and therapeutic development.
• Oleic acid binding regulates lipid accumulation and apoptosis in hepatocytes, with effects distinct from saturated fatty acids.
• Oleic acid binding to adrenaline protects against adrenaline-induced cardiac mitochondrial dysfunction.
• Oleic acid-mediated polyamine accumulation promotes endometrial cancer under metabolic syndrome conditions.
• Plasma and fecal metabolomics identify oleic acid as a functional metabolite in adenoma-colorectal cancer progression.
• Serum albumin is a primary non-covalent binding protein for nitro-oleic acid, a nitrated derivative of oleic acid.
• Odorant-binding proteins bind oleic acid to trigger behavioral responses in termites, showing evolutionary conservation of oleic acid binding.
• Oleic acid treatment of rice grains reduces starch digestibility through starch-lipid complex formation, relevant to food science.
• Interactive multiple binding of oleic acid with human serum albumin can be modulated by drugs such as warfarin and ibuprofen.
• Oleic acid binding is a druggable interface for modulating lipid signaling and metabolic pathways.
• CRISPR-based models enable causal testing of oleic acid binding proteins in disease contexts.
What Happens During oleic acid binding?
Oleic acid recognition and initial contact
In simple terms: The protein first recognizes and grabs onto oleic acid.
Oleic acid binding begins with the recognition of the fatty acid by a specific binding pocket or surface region on the target protein. This interaction is driven by hydrophobic and van der Waals forces, as oleic acid is a long-chain fatty acid with a cis double bond at position 9. For example, odorant-binding proteins in termites bind oleic acid to trigger burial behavior, demonstrating a specific recognition event. Serum albumin also binds oleic acid non-covalently, with multiple binding sites that can accommodate other ligands.
Conformational changes and complex stabilization
In simple terms: Once bound, the protein may change shape to hold oleic acid tightly.
Upon binding, the protein may undergo conformational changes that stabilize the oleic acid-protein complex. Isothermal titration calorimetry studies of oleic acid binding to adrenaline and heart mitochondria show that binding is associated with specific thermodynamic signatures, indicating structural rearrangements. In hepatocytes, oleic acid binding leads to differential lipid accumulation compared to palmitic acid, suggesting that the binding event triggers distinct downstream responses.
Downstream signaling and metabolic effects
In simple terms: The binding event sends signals or changes metabolism inside the cell.
Oleic acid binding can initiate signaling cascades or alter metabolic flux. In endometrial cancer, oleic acid-mediated polyamine accumulation promotes tumor growth under metabolic syndrome conditions, linking oleic acid binding to oncogenic metabolism. In colorectal cancer progression, oleic acid is identified as a functional metabolite, suggesting that its binding to cellular targets contributes to adenoma-carcinoma progression. In the heart, oleic acid binding to adrenaline ameliorates mitochondrial dysfunction, indicating a protective signaling role.
Regulation of oleic acid availability and binding
In simple terms: The amount of oleic acid and the proteins that bind it are controlled by the cell.
The availability of oleic acid for binding is regulated by lipid metabolism, including synthesis, uptake, and oxidation. Oleic acid treatment of rice grains reduces starch digestibility through formation of starch-lipid complexes, showing that oleic acid binding to macromolecules can alter their properties. In human serum, albumin acts as a primary non-covalent binding protein for nitro-oleic acid, and the presence of drugs such as warfarin and ibuprofen can modulate this binding. These examples illustrate that oleic acid binding is subject to competitive and environmental regulation.
Key Genes Involved in GO:0070538 oleic acid binding
The following genes and proteins are representative of oleic acid binding activity, based on published literature and functional annotations.
| Gene | Major Role | Research Relevance |
|---|---|---|
| FABP4 | Intracellular fatty acid chaperone that binds oleic acid | Metabolic syndrome, cancer, lipid trafficking |
| FABP5 | Binds oleic acid and other fatty acids | Lipid signaling, cancer progression |
| ALB | Serum albumin binds oleic acid non-covalently | Drug interactions, nitro-oleic acid transport |
| OBP | Odorant-binding protein binds oleic acid in termites | Behavioral studies, evolutionary conservation |
| CD36 | Membrane receptor for fatty acids including oleic acid | Lipid uptake, metabolic disease |
| PPARG | Nuclear receptor activated by fatty acids | Adipogenesis, insulin sensitivity |
| SCD1 | Desaturase that synthesizes oleic acid from stearic acid | Lipid metabolism, cancer |
| DGAT1 | Enzyme that esterifies oleic acid into triglycerides | Lipid storage, hepatosteatosis |
| CPT1A | Mitochondrial enzyme that binds oleic acid derivatives | Fatty acid oxidation, cardiac function |
| HSPA8 | Chaperone that interacts with oleic acid | Protein folding, lipid stress |
| LPL | Lipoprotein lipase binds and hydrolyzes oleic acid esters | Lipid processing, atherosclerosis |
| FABP1 | Liver fatty acid-binding protein binds oleic acid | Hepatic lipid metabolism |
| FABP3 | Heart-type fatty acid-binding protein binds oleic acid | Cardiac mitochondrial function |
| SLC27A1 | Fatty acid transport protein that facilitates oleic acid uptake | Metabolic disorders |
| ACSL1 | Acyl-CoA synthetase that activates oleic acid | Lipid synthesis, energy metabolism |
| PLIN1 | Perilipin binds oleic acid on lipid droplets | Lipid droplet dynamics |
| NR1H3 | Liver X receptor binds oxysterols and fatty acids | Cholesterol metabolism |
| PPARA | Peroxisome proliferator-activated receptor alpha binds fatty acids | Fatty acid oxidation, inflammation |
How Is oleic acid binding Regulated?
Oleic acid binding is regulated at multiple levels. The availability of oleic acid is controlled by enzymes such as SCD1, which desaturates stearic acid to oleic acid, and by dietary intake. Competitive binding by other ligands, such as warfarin and ibuprofen to serum albumin, can modulate oleic acid binding. In cancer, metabolic syndrome promotes oleic acid-mediated polyamine accumulation, suggesting that systemic metabolic status regulates oleic acid binding and downstream effects. Additionally, oleic acid treatment of rice grains alters starch digestibility through starch-lipid complex formation, indicating that binding can be influenced by the macromolecular environment.
oleic acid binding and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| FABP4 | Metabolic syndrome, cancer | Knockout and overexpression in cancer cell lines |
| ALB | Drug interactions, nitro-oleic acid transport | Point mutation to alter binding affinity |
| SCD1 | Lipid metabolism, hepatosteatosis | Knockout in hepatocytes |
| PPARG | Insulin resistance, adipogenesis | Knock-in of human variants |
| CD36 | Atherosclerosis, lipid uptake | Overexpression in macrophages |
Oleic acid binding in colorectal cancer
Integrative plasma and fecal metabolomics identify oleic acid as a functional metabolite in adenoma-colorectal cancer progression, suggesting that oleic acid binding proteins may contribute to early diagnostic biomarkers and disease mechanisms. The study highlights that oleic acid levels and its interactions are altered during cancer progression, making oleic acid binding a potential target for intervention.
Oleic acid binding in endometrial cancer and metabolic syndrome
Metabolic syndrome promotes endometrial cancer through oleic acid-mediated polyamine accumulation, linking oleic acid binding to oncogenic metabolic reprogramming. This suggests that proteins binding oleic acid may be involved in polyamine synthesis and tumor growth under metabolic syndrome conditions.
Oleic acid binding in cardiac mitochondrial dysfunction
Oleic acid ameliorates adrenaline-induced dysfunction of rat heart mitochondria by binding with adrenaline, as shown by isothermal titration calorimetry. This indicates that oleic acid binding can protect mitochondrial function and may have therapeutic implications for cardiac stress.
Oleic acid binding in hepatocyte lipid accumulation and apoptosis
Differential effects of oleic and palmitic acid on lipid accumulation and apoptosis in cultured hepatocytes demonstrate that oleic acid binding promotes lipid storage and reduces apoptosis compared to saturated fatty acids. This has implications for non-alcoholic fatty liver disease and metabolic disorders.
From oleic acid binding-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of FABP4 affect oleic acid binding and lipid accumulation? | FABP4 knockout cell line |
| Does a point mutation in albumin alter oleic acid binding affinity? | ALB point-mutation knock-in |
| Can overexpression of FABP5 increase oleic acid uptake? | FABP5 overexpression stable line |
| Does oleic acid binding to adrenaline protect mitochondria? | Cardiomyocyte knockout of binding partner |
| Is CD36 required for oleic acid-mediated signaling? | CD36 knockout in macrophages |
| Does SCD1 knockout reduce oleic acid synthesis and binding? | SCD1 knockout hepatocytes |
How to Study the oleic acid binding Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Isothermal titration calorimetry | Binding affinity and thermodynamics | Oleic acid binding to purified proteins |
| Fluorescence spectroscopy | Binding-induced fluorescence changes | Competitive binding with drugs |
| Lipidomics | Oleic acid and lipid species quantification | Cancer metabolomics |
| Metabolomics | Global metabolite profiling | Biomarker discovery |
| CRISPR knockout | Gene function loss | Causal testing of binding proteins |
| CRISPR point mutation | Specific amino acid changes | Binding site validation |
| CRISPR knock-in | Tagged or variant protein expression | Live-cell imaging of binding |
| Overexpression | Increased protein levels | Gain-of-function studies |
Isothermal titration calorimetry (ITC)
ITC measures the heat released or absorbed during oleic acid binding to a protein, providing thermodynamic parameters such as dissociation constant (Kd) and stoichiometry. This method was used to study oleic acid binding to adrenaline and heart mitochondria.
Fluorescence spectroscopy
Fluorescence spectroscopy can detect changes in intrinsic protein fluorescence upon oleic acid binding, as shown for human serum albumin interactions with oleic acid, warfarin, and ibuprofen. This method is suitable for determining binding affinities and competitive binding.
Lipidomics and metabolomics
Lipidomics and metabolomics quantify oleic acid and its metabolites in biological samples. Integrative plasma and fecal metabolomics identified oleic acid as a functional metabolite in colorectal cancer progression. These methods can reveal changes in oleic acid availability and binding partners.
CRISPR-based functional genomics
CRISPR knockout, point-mutation, knock-in, and overexpression models enable causal testing of genes involved in oleic acid binding. For example, knocking out FABP4 or SCD1 can reveal their roles in lipid accumulation and apoptosis.
How CRISPR Can Be Used to Study GO:0070538 oleic acid binding
Knockout
CRISPR knockout of genes encoding oleic acid binding proteins, such as FABP4 or SCD1, can determine whether these proteins are required for oleic acid-mediated effects on lipid accumulation and apoptosis. Knockout models are essential for loss-of-function studies.
Point Mutation
Point mutations can be introduced into the oleic acid binding pocket of proteins like serum albumin to alter binding affinity and specificity. This approach helps map critical residues for oleic acid binding and can validate structural predictions.
Knock-in
Knock-in of tagged versions of oleic acid binding proteins, such as GFP-FABP4, enables live-cell imaging and tracking of oleic acid binding dynamics. Knock-in of disease-associated variants can also model human mutations.
Overexpression
Overexpression of oleic acid binding proteins like FABP5 or CD36 can increase oleic acid uptake and reveal gain-of-function phenotypes in lipid metabolism and cancer progression.
How EDITGENE Supports oleic acid binding Research
Researchers studying oleic acid binding-related genes often need to determine whether a candidate gene is causally involved in lipid metabolism, cancer progression, or mitochondrial function. EDITGENE provides CRISPR-based cell model services to enable precise genetic perturbations and functional validation.
Contact EDITGENE today to design your custom CRISPR model for oleic acid binding research.
Frequently Asked Questions About oleic acid binding
What is oleic acid binding?
Oleic acid binding (GO:0070538) is a molecular function defined as binding to oleic acid, the 18-carbon monounsaturated fatty acid (9Z)-octadec-9-enoic acid.
What genes are involved in oleic acid binding?
Genes such as FABP4, FABP5, ALB, CD36, and SCD1 encode proteins that bind or regulate oleic acid.
What is GO:0070538?
GO:0070538 is the Gene Ontology identifier for the molecular function oleic acid binding.
How is oleic acid binding studied?
Methods include isothermal titration calorimetry, fluorescence spectroscopy, lipidomics, and CRISPR-based functional genomics.
What diseases are linked to oleic acid binding?
Colorectal cancer, endometrial cancer, metabolic syndrome, and cardiac mitochondrial dysfunction have been linked to oleic acid binding.
Does oleic acid binding affect apoptosis?
Yes, oleic acid binding differentially affects lipid accumulation and apoptosis in hepatocytes compared to palmitic acid.
Can CRISPR be used to study oleic acid binding?
Yes, CRISPR knockout, point mutation, knock-in, and overexpression models enable causal testing of oleic acid binding proteins.
What is the role of serum albumin in oleic acid binding?
Serum albumin is a primary non-covalent binding protein for oleic acid and nitro-oleic acid, and its binding can be modulated by drugs.
Is oleic acid binding conserved across species?
Yes, odorant-binding proteins in termites bind oleic acid to trigger behavior, indicating evolutionary conservation.
How does oleic acid binding affect mitochondria?
Oleic acid binding to adrenaline ameliorates adrenaline-induced mitochondrial dysfunction in rat heart.
Conclusion
Oleic acid binding (GO:0070538) is a fundamental molecular function with broad implications for lipid metabolism, cancer, and cardiac physiology. Proteins such as FABP4, FABP5, and serum albumin mediate these interactions, which can be studied using biophysical, omics, and CRISPR-based methods. Understanding oleic acid binding provides insights into disease mechanisms and potential therapeutic targets. EDITGENE offers comprehensive CRISPR services to accelerate research in this field.
References
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