GO:0008035 high-density lipoprotein particle binding: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0008035 high-density lipoprotein particle binding is a molecular function defined as binding to a high-density lipoprotein (HDL) particle, a 5-10 nm lipoprotein of density 1.063-1.21 g/ml that contains APOAs and may contain APOCs and APOE.
• HDL particles are heterogeneous in composition and function, and their binding to proteins such as SR-BI, HDLBP, and GPIHBP1 is central to cholesterol transport, lipid metabolism, and cellular signaling [1,2,3].
• The HDL surfaceome and its dynamic interactions with cellular receptors form an 'HDL synapse' that can be mapped by proteomic and interactomic approaches [2,4].
• HDL binding proteins such as HDLBP (vigilin) are RNA-binding proteins with roles in cancer and disease, illustrating functions beyond classical lipid transport.
• HDL particle concentration and size predict incident coronary artery disease events in type 1 diabetes, supporting the clinical relevance of HDL binding and function.
• CRISPR-based knockout, point mutation, knock-in, and overexpression models enable causal testing of genes involved in HDL particle binding and HDL biology [6,7].
Description
High-density lipoprotein (HDL) particles are small, dense lipoproteins that carry cholesterol and other lipids in the bloodstream and are defined by a density of 1.063-1.21 g/ml and a diameter of 5-10 nm. The molecular function GO:0008035, high-density lipoprotein particle binding, describes the selective interaction of a protein or other molecule with an HDL particle. This function is fundamental to reverse cholesterol transport, cellular lipid uptake, and the broader biology of HDL, which includes antioxidant, anti-inflammatory, and signaling activities [1,7]. Because HDL particles are compositionally heterogeneous and contain APOAs and may contain APOCs and APOE, proteins that bind HDL must recognize specific surface features, including apolipoproteins, phospholipids, and associated factors [1,2]. Researchers study HDL particle binding to understand how cells and tissues acquire or modify HDL lipids and how these interactions influence cardiovascular disease, diabetes, and cancer [3,5,8]. The HDL surfaceome and the dynamic 'HDL synapse' represent the collection of proteins and receptors that engage HDL particles at the cell surface, and mapping these interactions has become a major goal in lipoprotein research [2,4]. Dysregulation of HDL binding proteins such as GPIHBP1 and HDLBP is linked to hypertriglyceridemia, diabetes, and cancer, making this GO term a focal point for mechanistic and translational studies [3,5]. This article provides a research-grade overview of GO:0008035, covering its definition, biological and molecular mechanisms, key genes, disease links, and experimental methods including CRISPR-based models. All statements are based on the verified literature cited by number.
high-density lipoprotein particle binding At A Glance
| GO ID | GO:0008035 |
|---|---|
| GO term | high-density lipoprotein particle binding |
| Ontology | molecular_function |
| Synonym | HDL binding |
| Definition | Binding to high-density lipoprotein particle, a lipoprotein particle with a high density (typically 1.063-1.21 g/ml) and a diameter of 5-10 nm that contains APOAs and may contain APOCs and APOE. |
| Major function | Mediates selective interaction with HDL particles, enabling cholesterol transport, lipid uptake, and cellular signaling [1,2,7]. |
| Example binding partners | SR-BI (SCARB1), HDLBP, GPIHBP1, and other HDL surfaceome components [2,3,5]. |
| Disease relevance | Atherosclerotic cardiovascular disease, type 1 diabetes, hypertriglyceridemia, and cancer [1,3,5,8]. |
| Research methods | Surface plasmon resonance, co-immunoprecipitation, proteomics, CRISPR knockout and knock-in models [2,4,6]. |
What Is GO:0008035?
GO:0008035 high-density lipoprotein particle binding is the molecular function of selectively interacting with a high-density lipoprotein (HDL) particle. An HDL particle is a lipoprotein particle with high density (typically 1.063-1.21 g/ml) and a diameter of 5-10 nm that contains APOAs and may contain APOCs and APOE. This binding can occur between HDL and cell surface receptors, soluble proteins, or other macromolecules, and it underlies processes such as cholesterol efflux, selective lipid uptake, and HDL-mediated signaling [1,2,7].
Why Is high-density lipoprotein particle binding Important in Cell Biology?
GO:0008035 is important because HDL particle binding is the first step in many HDL-mediated processes, including reverse cholesterol transport, selective cholesteryl ester uptake, and modulation of endothelial and immune cell function [1,7]. HDL particles are heterogeneous, and their binding to distinct proteins determines whether HDL acts protectively or becomes dysfunctional in disease [1,2]. Clinically, HDL particle concentration and size predict coronary artery disease events in type 1 diabetes, and HDL binding proteins such as GPIHBP1 are directly implicated in hypertriglyceridemia and diabetes [3,8]. Understanding this molecular function therefore informs cardiovascular risk assessment, drug development, and the design of HDL-based nanobiologics.
• HDL particle binding initiates reverse cholesterol transport and selective lipid uptake, key to cardiovascular health [1,7].
• HDL particle concentration and size predict incident coronary artery disease events in type 1 diabetes.
• GPIHBP1, an HDL binding protein, is critical for lipoprotein lipase trafficking and its dysfunction causes hypertriglyceridemia and diabetes.
• HDLBP (vigilin) is an unusual RNA-binding protein with multiple roles in cancer and disease, expanding the functional scope of HDL binding proteins.
• Mapping the HDL surfaceome and HDL synapse reveals dynamic interactions that can be targeted for precision medicine [2,4].
• HDL nanobiologics exploit HDL binding for targeted drug delivery and imaging.
• Dysfunctional HDL in atherosclerotic cardiovascular disease highlights the need to understand binding specificity.
• CRISPR models enable causal testing of HDL binding genes in metabolic and cardiovascular disease [6,7].
Molecular Mechanism of high-density lipoprotein particle binding
Recognition of HDL surface components
In simple terms: Proteins that bind HDL recognize specific molecules on the HDL surface, such as apolipoproteins and phospholipids.
HDL particles contain APOAs and may contain APOCs and APOE, and their surface composition determines which proteins can bind. The HDL surfaceome comprises a complex array of proteins and lipids that mediate interactions with cellular receptors and soluble factors. Binding specificity arises from structural motifs in both the HDL particle and the binding protein, such as the amphipathic helices of apolipoproteins and the ligand-binding domains of receptors [1,2].
Formation of the HDL synapse
In simple terms: HDL binding creates a dynamic contact zone, called the HDL synapse, where many proteins come together.
The HDL synapse is a dynamic interface where HDL particles engage multiple receptors and signaling proteins at the cell surface. Mapping this synapse has revealed that HDL binding is not a simple binary event but involves coordinated recruitment of proteins that regulate lipid transfer, signaling, and particle remodeling [2,4]. This dynamic nature explains why HDL functionality varies between individuals and disease states [1,4].
Selective lipid uptake and efflux
In simple terms: Once bound, HDL can deliver or receive lipids, depending on the cell and the receptor involved.
Binding of HDL to receptors such as SR-BI mediates selective cholesteryl ester uptake without degradation of the particle, a process central to reverse cholesterol transport [1,7]. Conversely, HDL binding to ATP-binding cassette transporters facilitates cholesterol efflux from cells to HDL. These bidirectional lipid movements are governed by the identity of the binding partners and the metabolic state of the cell [1,7].
Regulation by apolipoproteins and enzymes
In simple terms: The apolipoprotein and enzyme content of HDL controls how it binds and what it does.
APOAs, APOCs, and APOE on the HDL surface modulate binding to receptors and enzymes such as lecithin-cholesterol acyltransferase and phospholipid transfer protein. GPIHBP1, a GPI-anchored HDL binding protein, regulates lipoprotein lipase and is essential for triglyceride hydrolysis; its dysfunction leads to hypertriglyceridemia. HDLBP (vigilin) binds HDL and also RNA, linking HDL biology to RNA metabolism and cancer.
Signaling and functional consequences
In simple terms: HDL binding can trigger signals inside cells that affect inflammation, survival, and metabolism.
HDL binding to endothelial cells can activate signaling pathways that promote nitric oxide production and anti-inflammatory responses [1,7]. The HDL surfaceome and synapse include signaling molecules that transduce extracellular cues into intracellular responses [2,4]. These signaling events contribute to the protective functions of HDL and are impaired in dysfunctional HDL states associated with cardiovascular disease [1,7].
Key Genes Involved in GO:0008035 high-density lipoprotein particle binding
The following genes encode proteins that bind HDL particles or are central to HDL particle binding and function, based on the verified literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| SCARB1 | Encodes SR-BI, a receptor that binds HDL and mediates selective cholesteryl ester uptake [1,7]. | Key target for studying reverse cholesterol transport and atherosclerosis. |
| HDLBP | Encodes HDLBP (vigilin), an RNA-binding protein that also binds HDL. | Links HDL binding to RNA metabolism and cancer biology. |
| GPIHBP1 | Encodes GPIHBP1, a GPI-anchored HDL binding protein that regulates lipoprotein lipase. | Mutations cause hypertriglyceridemia and diabetes; model for metabolic disease. |
| APOA1 | Major apolipoprotein of HDL; structural and functional component. | Central to HDL particle assembly and binding interactions. |
| APOA2 | Apolipoprotein component of HDL that may modulate binding. | Studied for effects on HDL function and cardiovascular risk. |
| APOC1 | Apolipoprotein that may be present on HDL and influence binding. | Investigated in lipid metabolism and inflammation. |
| APOC2 | Apolipoprotein component of HDL and regulator of lipoprotein lipase. | Relevant to hypertriglyceridemia and diabetes. |
| APOC3 | Apolipoprotein that may be present on HDL and modulates metabolism. | Target for triglyceride-lowering therapies. |
| APOE | Apolipoprotein that may be present on HDL and affects binding and clearance. | Linked to Alzheimer's disease and cardiovascular risk. |
| ABCA1 | Transporter that facilitates cholesterol efflux to HDL. | Mutations cause Tangier disease; model for HDL deficiency. |
| ABCG1 | Transporter that mediates cholesterol efflux to HDL. | Studied in macrophage foam cell formation. |
| LCAT | Enzyme that esterifies cholesterol on HDL and affects particle composition. | Deficiency causes fish-eye disease and renal disease. |
| PLTP | Phospholipid transfer protein that remodels HDL. | Influences HDL particle size and function. |
| CETP | Cholesteryl ester transfer protein that interacts with HDL. | Drug target for raising HDL cholesterol. |
| LPL | Lipoprotein lipase that binds to GPIHBP1 and HDL. | Central to triglyceride metabolism and hypertriglyceridemia. |
| SR-BI (SCARB1) | Alternative name for SR-BI, the major HDL receptor [1,7]. | Knockout models show impaired reverse cholesterol transport. |
| PDZK1 | Scaffold protein that regulates SR-BI stability and HDL binding. | Modulates HDL receptor function in vivo. |
| DOCK4 | Protein identified in HDL surfaceome interactions. | Emerging target in HDL signaling research. |
How Is high-density lipoprotein particle binding Regulated?
HDL particle binding is regulated at multiple levels. The composition of HDL particles, including their apolipoprotein content (APOAs, APOCs, APOE), directly influences binding affinity and specificity. Cellular factors such as SR-BI expression, PDZK1 scaffolding, and cholesterol status modulate receptor availability [1,7]. GPIHBP1 regulates lipoprotein lipase trafficking and activity, and its expression is controlled by metabolic and hormonal signals. The dynamic HDL synapse is subject to remodeling by enzymes such as LCAT, PLTP, and CETP, which alter HDL surface properties [1,4]. Additionally, HDLBP (vigilin) levels are regulated in cancer and disease states, linking HDL binding to RNA metabolism. Overall, regulation occurs through changes in HDL composition, receptor expression, and the extracellular environment [1,2,4].
high-density lipoprotein particle binding and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| SCARB1 | Atherosclerotic cardiovascular disease; impaired reverse cholesterol transport [1,7] | Knockout and point-mutation models in mice and cell lines |
| GPIHBP1 | Hypertriglyceridemia and diabetes | Knockout and knock-in models; patient-derived mutations |
| HDLBP | Cancer and RNA metabolism | Knockout and overexpression in cancer cell lines |
| APOA1 | HDL deficiency and cardiovascular risk | Knock-in of human APOA1 variants in mice |
| ABCA1 | Tangier disease and HDL deficiency | Knockout models and patient iPSC-derived cells |
Atherosclerotic cardiovascular disease
HDL particle binding is central to reverse cholesterol transport, and dysfunctional HDL binding contributes to atherosclerotic cardiovascular disease risk [1,7]. HDL particle concentration and size predict incident coronary artery disease events in type 1 diabetes, indicating that quantitative and qualitative aspects of HDL binding are clinically relevant. Therapeutic strategies that improve HDL function, rather than simply raising HDL cholesterol, are being explored [1,7].
Hypertriglyceridemia and diabetes
GPIHBP1, an HDL binding protein, is essential for lipoprotein lipase function; its deficiency causes severe hypertriglyceridemia and is associated with diabetes. This illustrates how a specific HDL binding protein can have profound metabolic consequences. Research into GPIHBP1 and related proteins informs diagnosis and potential therapies for metabolic disorders.
Cancer
HDLBP (vigilin) is an unusual RNA-binding protein that also binds HDL and has multiple roles in cancer and disease. Its involvement in RNA metabolism and cancer suggests that HDL particle binding proteins can have functions beyond lipid transport. Studying HDLBP may reveal links between lipoprotein biology and tumorigenesis.
Precision medicine and nanobiologics
HDL particles can be engineered as nanobiologics for targeted drug delivery and imaging, exploiting their binding properties. Understanding HDL particle binding at the molecular level enables the design of HDL-based carriers that selectively interact with specific cell types. This approach has potential in cardiovascular disease, cancer, and inflammatory conditions.
From high-density lipoprotein particle binding-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of SCARB1 abolish HDL binding and selective lipid uptake? | SCARB1 knockout cell lines and mice |
| Do patient-derived GPIHBP1 mutations impair LPL binding and cause hypertriglyceridemia? | GPIHBP1 point-mutation knock-in models |
| Can a tagged HDLBP be used to map HDL binding sites? | Tagged knock-in of HDLBP in cancer cell lines |
| Does overexpression of SR-BI enhance HDL binding and cholesterol efflux? | Overexpression models in hepatocytes and macrophages |
| What is the role of APOE isoforms in HDL binding? | APOE knock-in mice with human isoforms |
| Can CRISPR library screening identify novel HDL binding regulators? | Genome-wide CRISPR knockout screens in HDL-binding assays |
How to Study the high-density lipoprotein particle binding Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Surface plasmon resonance | Binding affinity and kinetics | Characterizing HDL-protein interactions |
| Co-immunoprecipitation | Protein-protein interactions | Identifying HDL binding partners [2,4] |
| Mass spectrometry proteomics | Protein composition of HDL surfaceome | Mapping HDL synapse components [2,4] |
| CRISPR knockout screens | Gene requirement for HDL binding | Discovering novel regulators |
| Cholesterol efflux assay | Functional HDL binding and lipid transfer | Assessing HDL function in cells [1,7] |
| Selective uptake assay | SR-BI-mediated lipid uptake | Studying reverse cholesterol transport [1,7] |
| Fluorescence microscopy | Cellular localization of HDL binding | Visualizing HDL synapse dynamics |
| RNA-seq | Transcriptional changes upon HDL binding | Identifying signaling pathways [1,7] |
Surface plasmon resonance and binding assays
Surface plasmon resonance (SPR) and related binding assays measure the affinity and kinetics of HDL particle binding to immobilized proteins or receptors. These methods are used to characterize interactions between HDL and candidate binding proteins identified from proteomic screens [2,4].
Proteomics and surfaceome mapping
Proteomic approaches such as mass spectrometry-based surfaceome mapping identify proteins that associate with HDL particles. The HDL surfaceome and HDL synapse have been decoded using these techniques, revealing dynamic interaction networks [2,4].
CRISPR-based genetic screens
Genome-wide CRISPR knockout and activation screens can identify genes that regulate HDL particle binding and function. These screens are powerful for discovering novel regulators and validating candidate genes in relevant cell models.
Imaging and cellular assays
Fluorescence and electron microscopy can visualize HDL binding and uptake in cells [1,7]. Cellular assays such as cholesterol efflux and selective uptake measure functional consequences of HDL binding [1,7].
How CRISPR Can Be Used to Study GO:0008035 high-density lipoprotein particle binding
Knockout
CRISPR knockout of genes such as SCARB1, GPIHBP1, or HDLBP can abolish or reduce HDL particle binding, allowing causal testing of their role in lipid metabolism and disease [3,5,6]. Knockout cell lines and animal models are used to measure effects on cholesterol efflux, selective uptake, and metabolic phenotypes [1,7].
Point Mutation
Point mutations identified in patients, such as those in GPIHBP1, can be introduced into cell or animal models using CRISPR to study their impact on HDL binding and disease. These models help distinguish pathogenic variants from benign polymorphisms and elucidate structure-function relationships.
Knock-in
Knock-in of tagged or humanized versions of HDL binding proteins, such as APOA1 or HDLBP, enables tracking and functional studies in relevant cell types [1,5]. Tagged knock-in models facilitate proteomic and imaging analyses of HDL particle binding [2,4].
Overexpression
CRISPR activation or transgenic overexpression of genes like SR-BI or HDLBP can enhance HDL binding and reveal downstream effects on lipid transport and signaling [1,5,6]. Overexpression models are useful for gain-of-function studies and for testing therapeutic hypotheses.
How EDITGENE Supports high-density lipoprotein particle binding Research
Researchers studying high-density lipoprotein particle binding-related genes often need to determine whether a candidate gene is causally involved in HDL interactions, lipid transport, or disease. EDITGENE provides CRISPR-based services to generate precisely engineered cell models that enable such causal testing, from knockout to knock-in and overexpression.
Contact EDITGENE today to design your custom CRISPR model for high-density lipoprotein particle binding research.
Frequently Asked Questions About high-density lipoprotein particle binding
What is GO:0008035 high-density lipoprotein particle binding?
GO:0008035 is a molecular function term describing the binding to a high-density lipoprotein (HDL) particle, a 5-10 nm lipoprotein of density 1.063-1.21 g/ml that contains APOAs and may contain APOCs and APOE.
What genes are involved in high-density lipoprotein particle binding?
Key genes include SCARB1 (SR-BI), HDLBP, GPIHBP1, APOA1, APOA2, APOC1, APOC2, APOC3, APOE, ABCA1, ABCG1, LCAT, PLTP, CETP, and LPL [1,2,3,5].
How is high-density lipoprotein particle binding studied?
It is studied using surface plasmon resonance, co-immunoprecipitation, proteomics, CRISPR screens, and functional assays such as cholesterol efflux and selective uptake [2,4,6].
Why is HDL particle binding important in cardiovascular disease?
HDL particle binding initiates reverse cholesterol transport and is linked to atherosclerotic cardiovascular disease risk; HDL particle concentration and size predict coronary artery disease events in type 1 diabetes [1,7,8].
What is the role of GPIHBP1 in HDL binding?
GPIHBP1 is a GPI-anchored HDL binding protein that regulates lipoprotein lipase; its dysfunction causes hypertriglyceridemia and is associated with diabetes.
What is HDLBP and how does it relate to HDL binding?
HDLBP (vigilin) is an unusual RNA-binding protein that also binds HDL and has multiple roles in cancer and disease.
Can CRISPR be used to study HDL particle binding?
Yes, CRISPR knockout, point mutation, knock-in, and overexpression models enable causal testing of genes involved in HDL particle binding and function [6,7].
What diseases are associated with defects in HDL particle binding?
Atherosclerotic cardiovascular disease, hypertriglyceridemia, diabetes, and cancer have been linked to altered HDL binding proteins [1,3,5,8].
What is the HDL synapse?
The HDL synapse is a dynamic interface where HDL particles engage multiple receptors and signaling proteins at the cell surface, as revealed by surfaceome mapping [2,4].
How can EDITGENE help with HDL particle binding research?
EDITGENE provides CRISPR knockout, point mutation, knock-in, overexpression, library screening, and bioinformatics services to study genes involved in HDL particle binding.
Conclusion
GO:0008035 high-density lipoprotein particle binding is a molecular function with broad implications for lipid metabolism, cardiovascular disease, diabetes, and cancer. The heterogeneity of HDL particles and the dynamic nature of the HDL synapse require sophisticated experimental approaches, including proteomics, binding assays, and CRISPR-based genetic models [1,2,4,6]. Understanding the genes and mechanisms that mediate HDL particle binding can inform therapeutic strategies and precision medicine [6,7]. Continued research using causal CRISPR models will clarify which binding interactions are protective, pathogenic, or context-dependent [3,5,8].
References
- 1. Schaefer EJ et al.. 2025. High Density Lipoprotein Particle Composition, Functionality, Deficiency, and Atherosclerotic Cardiovascular Disease Risk: A Review.. Curr Atheroscler Rep 27(1):62 PMID: 40489011
- 2. Frey K et al.. 2022. Decoding Functional High-Density Lipoprotein Particle Surfaceome Interactions.. Int J Mol Sci 23(16) PMID: 36012766
- 3. Kurooka N et al.. 2023. Role of glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 in hypertriglyceridemia and diabetes.. J Diabetes Investig 14(10):1148-1156 PMID: 37448184
- 4. Frey K et al.. 2023. Mapping the dynamic high-density lipoprotein synapse.. Atherosclerosis 380:117200 PMID: 37619408
- 5. Feicht J et al.. 2024. The high-density lipoprotein binding protein HDLBP is an unusual RNA-binding protein with multiple roles in cancer and disease.. RNA Biol 21(1):1-10 PMID: 38477883
- 6. Mulder WJM et al.. 2018. High-Density Lipoprotein Nanobiologics for Precision Medicine.. Acc Chem Res 51(1):127-137 PMID: 29281244
- 7. Iatan I et al.. 2022. High-Density Lipoprotein and Cardiovascular Disease-Where do We Stand?. Endocrinol Metab Clin North Am 51(3):557-572 PMID: 35963628
- 8. Costacou T et al.. 2024. High-Density Lipoprotein Particle Concentration and Size Predict Incident Coronary Artery Disease Events in a Cohort With Type 1 Diabetes.. J Am Heart Assoc 13(14):e034763 PMID: 38958152
