GO:0036042 long-chain fatty acyl-CoA binding: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0036042 (long-chain fatty acyl-CoA binding) is a molecular function describing the binding of long-chain fatty acyl-CoA esters (13-22 carbon acyl chains) to proteins.
• Long-chain fatty acyl-CoAs are central intermediates in fatty acid oxidation, lipid synthesis, and protein acylation, and their binding proteins regulate energy metabolism and gene expression.
• Key proteins that bind long-chain fatty acyl-CoAs include ACSL1, ACBP, MCL-1, TANK-binding kinase 1 (TBK1), and zDHHC acyltransferases.
• Dysregulation of long-chain fatty acyl-CoA binding is linked to lipotoxicity, metabolic disorders, cancer, and neurodegeneration.
• AMPK senses long-chain fatty acyl-CoA esters to regulate energy homeostasis, making this binding function critical for metabolic signaling.
• CRISPR-based models (knockout, point mutation, knock-in, overexpression) enable precise interrogation of genes encoding long-chain fatty acyl-CoA binding proteins.
Description
Long-chain fatty acyl-CoA binding (GO:0036042) is a molecular function defined as the binding to a long-chain fatty acyl-CoA, any derivative of coenzyme A in which the sulfhydryl group is in a thioester linkage with a long-chain fatty-acyl group (13 to 22 carbons). This function is essential for cellular lipid metabolism, as long-chain fatty acyl-CoAs serve as substrates for beta-oxidation, membrane lipid synthesis, and protein acylation. Proteins that bind these esters regulate their availability, trafficking, and signaling roles, thereby influencing energy homeostasis and gene expression. Researchers study GO:0036042 to understand metabolic diseases, cancer, and neurodegenerative conditions where lipid metabolism is perturbed. The binding event itself is not merely a passive interaction; it often triggers conformational changes or allosteric regulation in enzymes and transcription factors. For example, acyl-CoA-binding proteins (ACBPs) bridge long-chain acyl-CoA metabolism to gene regulation in plants and animals. In humans, ACSL1 and MCL-1 interaction promotes fatty acid oxidation, highlighting the importance of acyl-CoA binding in mitochondrial function. Thus, GO:0036042 represents a critical node in lipid signaling and metabolic control.
long-chain fatty acyl-CoA binding At A Glance
| GO ID | GO:0036042 |
|---|---|
| GO term | long-chain fatty acyl-CoA binding |
| Ontology | molecular_function |
| Synonym | long-chain fatty acyl-coenyme A binding |
| Definition | Binding to a long-chain fatty acyl-CoA, any derivative of coenzyme A in which the sulfhydryl group is in a thioester linkage with a long-chain fatty-acyl group. A long-chain fatty acid has an aliphatic tail containing 13 to 22 carbons. |
| Major function | Binding of long-chain fatty acyl-CoA esters for metabolism, transport, and signaling |
| Related processes | Fatty acid beta-oxidation, lipid biosynthesis, protein acylation, energy sensing |
| Key regulators | ACSL1, ACBP, AMPK, MCL-1, TBK1, zDHHC enzymes |
What Is GO:0036042?
GO:0036042, long-chain fatty acyl-CoA binding, is the molecular function of selectively interacting with a long-chain fatty acyl-CoA molecule. A long-chain fatty acyl-CoA is a coenzyme A derivative where the sulfhydryl group forms a thioester bond with a fatty acid containing 13 to 22 carbons. This binding can be non-covalent and reversible, and it is distinct from enzymatic catalysis. The term encompasses proteins that sense, transport, or utilize these esters in metabolic and signaling pathways.
Why Is long-chain fatty acyl-CoA binding Important in Cell Biology?
Long-chain fatty acyl-CoA binding is important because it controls the fate of fatty acids in cells, from energy production to membrane remodeling and signaling. Proteins that bind these esters are involved in metabolic diseases such as obesity, diabetes, and non-alcoholic fatty liver disease, as well as cancer and neurodegeneration. Understanding this function can reveal therapeutic targets and biomarkers for lipid-related disorders.
• Regulates fatty acid oxidation and energy homeostasis.
• Mediates lipotoxicity and cellular stress responses.
• Controls protein acylation and membrane targeting.
• Links lipid metabolism to gene expression via ACBPs.
• Involved in cancer cell survival through MCL-1 and ACSL1.
• Modulates immune signaling via TBK1 and ACSL1.
• Serves as a sensor for AMPK energy signaling.
• Potential target for metabolic disease therapeutics.
• Impacts mitochondrial function and apoptosis.
• Relevant to plant and microbial lipid metabolism.
Molecular Mechanism of long-chain fatty acyl-CoA binding
Substrate Recognition and Binding Pocket
In simple terms: Proteins have a pocket that fits long-chain fatty acyl-CoAs like a lock and key.
Long-chain fatty acyl-CoA binding proteins possess hydrophobic pockets that accommodate the acyl chain and a hydrophilic region that interacts with the CoA moiety. For example, acyl-CoA-binding proteins (ACBPs) use a conserved domain to bind acyl-CoAs with high affinity. The binding is reversible and can be competed by other acyl-CoA species.
Conformational Changes and Allosteric Regulation
In simple terms: Binding can change the shape of the protein, turning its activity on or off.
Upon binding, proteins such as AMPK undergo conformational changes that modulate kinase activity. Similarly, ACSL1 binding to long-chain acyl-CoAs affects its localization and interaction with MCL-1. These allosteric effects are critical for metabolic signaling.
Role in Enzymatic Catalysis and Transport
In simple terms: Some proteins use the bound acyl-CoA as a substrate to make other molecules or move it around.
Enzymes like ACSL1 ligate long-chain fatty acids to CoA, and the product remains bound for channeling into beta-oxidation or lipid synthesis. zDHHC acyltransferases utilize long-chain acyl-CoAs for protein palmitoylation, demonstrating a direct role in modification reactions.
Regulation by Energy Sensors
In simple terms: Energy sensors like AMPK check acyl-CoA levels to adjust metabolism.
AMPK directly senses long-chain fatty acyl-CoA esters, leading to changes in downstream metabolic pathways. TBK1 regulates ACSL1 localization, thereby controlling hepatic fatty acid oxidation. This feedback ensures energy balance.
Key Genes Involved in GO:0036042 long-chain fatty acyl-CoA binding
The following genes encode proteins that bind long-chain fatty acyl-CoAs or regulate their metabolism, as supported by published literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| ACSL1 | Activates long-chain fatty acids to acyl-CoAs | Fatty acid oxidation, cancer metabolism |
| ACBP | Binds and transports acyl-CoAs | Gene regulation, lipid signaling |
| MCL-1 | Anti-apoptotic protein, interacts with ACSL1 | Promotes fatty acid oxidation, cancer survival |
| TBK1 | Regulates ACSL1 localization | Hepatic fatty acid oxidation, immune signaling |
| AMPK | Senses acyl-CoA esters | Energy homeostasis, metabolic regulation |
| zDHHC | Protein acyltransferases using acyl-CoAs | Palmitoylation, membrane targeting |
| CPT1A | Mitochondrial beta-oxidation entry | Fatty acid oxidation |
| ACADM | Beta-oxidation enzyme | Mitochondrial fatty acid oxidation |
| HADHA | Beta-oxidation trifunctional protein | Fatty acid oxidation |
| SLC25A20 | Carnitine-acylcarnitine translocase | Fatty acid transport |
| ACOX1 | Peroxisomal beta-oxidation | Lipid metabolism |
| FASN | Fatty acid synthesis | Lipogenesis |
| SCD1 | Desaturase | Lipid metabolism |
| PPARA | Transcription factor | Regulates lipid metabolism genes |
| SREBF1 | Transcription factor | Lipogenesis regulation |
| NR1H3 | Liver X receptor | Cholesterol and lipid metabolism |
| DGAT1 | Diacylglycerol acyltransferase | Triglyceride synthesis |
How Is long-chain fatty acyl-CoA binding Regulated?
Long-chain fatty acyl-CoA binding is regulated at multiple levels. AMPK senses acyl-CoA esters to modulate energy metabolism. TBK1 controls the localization of ACSL1, affecting fatty acid oxidation. ACBPs can translocate to the nucleus and influence gene expression in response to acyl-CoA levels. Additionally, MCL-1 interaction with ACSL1 enhances fatty acid oxidation under stress.
long-chain fatty acyl-CoA binding and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| ACSL1 | Hepatic steatosis, cancer | Liver-specific knockout mouse |
| MCL-1 | Cancer survival | Knockout cell lines |
| TBK1 | Metabolic syndrome | Point mutation knock-in |
| ACBP | Neurodegeneration | Overexpression in neurons |
| AMPK | Diabetes, obesity | Knockout models |
Metabolic Disorders and Lipotoxicity
Dysregulated long-chain fatty acyl-CoA binding contributes to lipotoxicity, a condition where excess fatty acids cause cellular damage. This is implicated in obesity, insulin resistance, and non-alcoholic fatty liver disease. TBK1-mediated regulation of ACSL1 is critical for hepatic fatty acid oxidation, and its disruption leads to lipid accumulation.
Cancer Metabolism
Cancer cells often reprogram lipid metabolism to support growth. MCL-1 promotes long-chain fatty acid oxidation through interaction with ACSL1, providing energy and survival advantages. Targeting this interaction may be a therapeutic strategy.
Neurodegeneration and Lipid Signaling
Long-chain fatty acyl-CoAs are involved in neuronal membrane homeostasis and signaling. ACBPs in the brain regulate acyl-CoA pools, and their dysfunction has been linked to neurodegenerative conditions. However, direct evidence in humans is still emerging.
From long-chain fatty acyl-CoA binding-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does ACSL1 binding to acyl-CoA affect beta-oxidation? | ACSL1 knockout hepatocytes |
| How does MCL-1 interaction with ACSL1 promote cancer? | MCL-1 knockout cancer cells |
| What is the role of AMPK sensing of acyl-CoAs? | AMPK point mutant knock-in |
| How does ACBP regulate gene expression? | ACBP overexpression in cell lines |
| Does zDHHC palmitoylation depend on acyl-CoA binding? | zDHHC knockout |
| Can TBK1 localization be altered by point mutations? | TBK1 knock-in mutations |
How to Study the long-chain fatty acyl-CoA binding Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Lipidomics (LC-MS) | Acyl-CoA species abundance | Metabolic profiling |
| ITC | Binding affinity (Kd) | Protein-lipid interactions |
| SPR | Binding kinetics | Real-time interaction |
| CRISPR knockout screen | Gene essentiality | Functional genomics |
| Immunofluorescence | Protein localization | Subcellular distribution |
| Western blot | Protein expression | Validation of knockouts |
| RNA-seq | Transcriptional changes | Gene expression profiling |
Lipidomics and Acyl-CoA Profiling
Mass spectrometry-based lipidomics can quantify long-chain fatty acyl-CoA species in cells and tissues, revealing changes upon genetic perturbation. This method is essential for validating binding and metabolism.
Protein-Lipid Interaction Assays
Techniques such as isothermal titration calorimetry (ITC) and surface plasmon resonance (SPR) measure binding affinity between proteins and long-chain acyl-CoAs. These assays confirm direct binding and kinetics.
CRISPR Screens and Functional Genomics
Genome-wide CRISPR knockout screens can identify genes required for long-chain fatty acyl-CoA binding and downstream phenotypes. This approach links genotype to metabolic function.
Imaging and Subcellular Localization
Fluorescence microscopy with tagged proteins (e.g., GFP-ACSL1) reveals localization changes upon acyl-CoA binding. Live-cell imaging can track dynamic interactions.
How CRISPR Can Be Used to Study GO:0036042 long-chain fatty acyl-CoA binding
Knockout
CRISPR knockout of genes encoding long-chain fatty acyl-CoA binding proteins (e.g., ACSL1, ACBP) can reveal their roles in fatty acid oxidation and lipid homeostasis. Knockout cell lines are valuable for metabolic assays.
Point Mutation
Introducing point mutations in binding pockets (e.g., AMPK, TBK1) can dissect the contribution of acyl-CoA binding to protein function without abolishing expression. This is useful for separating binding from other activities.
Knock-in
Knock-in of tagged versions (e.g., GFP-ACSL1) allows visualization and pull-down of binding complexes. This approach preserves endogenous regulation.
Overexpression
Overexpression of ACBP or ACSL1 can model gain-of-function states and test sufficiency in lipid signaling. It is often used in cell-based assays.
How EDITGENE Supports long-chain fatty acyl-CoA binding Research
Researchers studying long-chain fatty acyl-CoA binding-related genes often need to determine whether a candidate gene is causally involved in metabolic phenotypes. EDITGENE provides comprehensive CRISPR services to generate precise cellular models for such investigations.
Contact EDITGENE today to design your custom CRISPR model for long-chain fatty acyl-CoA binding research.
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DBI Knockout HEK293 Cell Line | EDJ-KQ2682 | Human | 1622 | Details Get a Quote |
| FABP1 Knockout HEK293 Cell Line | EDJ-KQ3052 | Human | 2168 | Details Get a Quote |
| SCP2 Knockout HEK293 Cell Line | EDJ-KQ5722 | Human | 6342 | Details Get a Quote |
| ACOT7 Knockout HEK293 Cell Line | EDJ-KQ7375 | Human | 11332 | Details Get a Quote |
| PNPLA3 Knockout HEK293 Cell Line | EDJ-KQ14822 | Human | 80339 | Details Get a Quote |
| SCP2 Knockout A-549 Cell Line | EDJ-KQ29111 | Human | 6342 | Details Get a Quote |
| SCP2 Knockout HCT 116 Cell Line | EDJ-KQ29112 | Human | 6342 | Details Get a Quote |
| SCP2 Knockout HeLa Cell Line | EDJ-KQ29113 | Human | 6342 | Details Get a Quote |
| DBI Knockout A-549 Cell Line | EDJ-KQ23489 | Human | 1622 | Details Get a Quote |
| DBI Knockout HCT 116 Cell Line | EDJ-KQ23490 | Human | 1622 | Details Get a Quote |
| DBI Knockout HeLa Cell Line | EDJ-KQ23491 | Human | 1622 | Details Get a Quote |
| ACOT7 Knockout A-549 Cell Line | EDJ-KQ32496 | Human | 11332 | Details Get a Quote |
| ACOT7 Knockout HCT 116 Cell Line | EDJ-KQ32497 | Human | 11332 | Details Get a Quote |
| ACOT7 Knockout HeLa Cell Line | EDJ-KQ32498 | Human | 11332 | Details Get a Quote |
| PNPLA3 Knockout A-549 Cell Line | EDJ-KQ45254 | Human | 80339 | Details Get a Quote |
Displaying Records 1 To 15 Of 21 Records
Frequently Asked Questions About long-chain fatty acyl-CoA binding
What is long-chain fatty acyl-CoA binding?
It is a molecular function (GO:0036042) where a protein binds to a long-chain fatty acyl-CoA, a coenzyme A derivative with a 13-22 carbon fatty acid.
What genes are involved in long-chain fatty acyl-CoA binding?
Key genes include ACSL1, ACBP, MCL-1, TBK1, AMPK, and zDHHC family members.
What is the GO ID for long-chain fatty acyl-CoA binding?
The GO ID is GO:0036042.
How is long-chain fatty acyl-CoA binding regulated?
It is regulated by energy sensors like AMPK, and by proteins such as TBK1 that control localization of ACSL1.
What diseases are associated with long-chain fatty acyl-CoA binding?
Dysregulation is linked to lipotoxicity, metabolic disorders, cancer, and neurodegeneration.
What methods are used to study long-chain fatty acyl-CoA binding?
Common methods include lipidomics, ITC, SPR, CRISPR screens, and imaging.
What is the role of ACSL1 in long-chain fatty acyl-CoA binding?
ACSL1 activates long-chain fatty acids to acyl-CoAs and interacts with MCL-1 to promote fatty acid oxidation.
How does AMPK sense long-chain fatty acyl-CoAs?
AMPK binds long-chain fatty acyl-CoA esters, leading to conformational changes that regulate its kinase activity.
Can CRISPR be used to study long-chain fatty acyl-CoA binding?
Yes, CRISPR knockout, point mutation, knock-in, and overexpression models are powerful tools for dissecting gene function in this pathway.
What is the synonym for GO:0036042?
The synonym is long-chain fatty acyl-coenyme A binding.
Conclusion
Long-chain fatty acyl-CoA binding (GO:0036042) is a fundamental molecular function that governs lipid metabolism, energy sensing, and cellular signaling. Its dysregulation contributes to major human diseases, making it a compelling target for research. By leveraging CRISPR-based models and advanced analytical methods, scientists can uncover precise mechanisms and develop therapeutic strategies. EDITGENE supports these efforts with tailored gene editing and screening services.
References
- 1. Nakamura MT et al.. 2014. Regulation of energy metabolism by long-chain fatty acids.. Prog Lipid Res 53:124-44 PMID: 24362249
- 2. Engin AB. 2017. What Is Lipotoxicity?. Adv Exp Med Biol 960:197-220 PMID: 28585200
- 3. Wright T et al.. 2024. Anti-apoptotic MCL-1 promotes long-chain fatty acid oxidation through interaction with ACSL1.. Mol Cell 84(7):1338-1353.e8 PMID: 38503284
- 4. Wundersitz A et al.. 2025. Acyl-CoA-binding proteins: bridging long-chain acyl-CoA metabolism to gene regulation.. New Phytol 246(5):1960-1966 PMID: 40259851
- 5. Desjardins EM et al.. 2025. Sensing of Long-Chain Fatty Acyl-CoA Esters by AMPK.. Methods Mol Biol 2882:121-137 PMID: 39992507
- 6. Huh JY et al.. 2020. TANK-Binding Kinase 1 Regulates the Localization of Acyl-CoA Synthetase ACSL1 to Control Hepatic Fatty Acid Oxidation.. Cell Metab 32(6):1012-1027.e7 PMID: 33152322
- 7. Adeva-Andany MM et al.. 2019. Mitochondrial β-oxidation of saturated fatty acids in humans.. Mitochondrion 46:73-90 PMID: 29551309
- 8. Puthenveetil R et al.. 2022. Access and utilization of long chain fatty acyl-CoA by zDHHC protein acyltransferases.. Curr Opin Struct Biol 77:102463 PMID: 36183446
