GO:0062136 low-density lipoprotein receptor complex: Components, Assembly and Research Methods, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0062136 defines the low-density lipoprotein receptor complex, a plasma membrane protein complex with LDL particle receptor activity that can also bind xenobiotic toxins and deliver them into the cell via endocytosis.
• The complex is best exemplified by LDLR, which binds apolipoprotein B100 on LDL particles; the recent structure of apoB100 bound to LDLR reveals the molecular basis of this interaction.
• After endocytosis, most substrates are degraded in the endosome while the receptor recycles to the plasma membrane; PCSK9 disrupts this recycling by preventing SNX17-mediated LDLR recycling.
• LDLR family members are not only metabolic receptors but also entry receptors for viruses such as yellow fever virus and Semliki Forest virus, and they are recognized by VSV glycoprotein [5,7,8].
• The LDLR-mTORC1 axis coordinates CD8+ T cell activation, linking lipoprotein receptor function to immune signaling.
• CRISPR-based knockout, point mutation, knock-in, and overexpression models are essential to dissect the assembly, trafficking, and signaling functions of the low-density lipoprotein receptor complex [1,6].
Description
The low-density lipoprotein receptor complex (GO:0062136) is a plasma membrane protein complex capable of low-density lipoprotein particle receptor activity. It is a central component of cellular cholesterol homeostasis and also serves as a binding site for xenobiotic toxins, delivering them into the cell via endocytosis. While most substrates are degraded in the endosome, the receptor recycles to the plasma membrane, and it may also act as a transducer of intracellular signal pathways in cooperation with other cell-surface receptors. The complex is best known for the LDL receptor (LDLR), which binds apolipoprotein B100 (apoB100) on LDL particles; the 2025 structure of apoB100 bound to LDLR has provided unprecedented detail on this interaction. Beyond cholesterol uptake, LDLR family members participate in diverse biological processes, including Wnt/beta-catenin signaling, immune cell activation through the LDLR-mTORC1 axis, and viral entry [5,7,8]. Researchers study this complex to understand atherosclerosis, viral pathogenesis, and metabolic regulation, and to develop therapeutic strategies targeting receptor trafficking and signaling [3,6].
low-density lipoprotein receptor complex At A Glance
| GO ID | GO:0062136 |
|---|---|
| GO term | low-density lipoprotein receptor complex |
| Ontology | cellular_component |
| Synonym | LDLR complex; LDL receptor complex; low-density lipoprotein particle receptor complex |
| Major function | Low-density lipoprotein particle receptor activity; binds xenobiotic toxins; mediates endocytosis; receptor recycling; signal transduction |
| Cellular location | Plasma membrane |
| Associated processes | Endocytosis, endosomal degradation, receptor recycling, intracellular signaling |
| Representative gene | LDLR (low-density lipoprotein receptor) |
| Related family members | VLDLR, LRP1, LRP5/6, ApoER2 |
What Is GO:0062136?
According to the QuickGO definition, GO:0062136 (low-density lipoprotein receptor complex) is a plasma membrane protein complex capable of low-density lipoprotein particle receptor activity. It may also bind xenobiotic toxins and deliver them into the cell via endocytosis. While most substrates get degraded via the endosome, the receptor is recycled to the plasma membrane. It may also act as a transducer of intracellular signal pathways and often acts in cooperation with other cell-surface receptors. In simpler terms, it is a cell-surface receptor machine that captures LDL particles and other ligands, internalizes them, and then recycles back to the surface, while also participating in signal transduction.
Why Is low-density lipoprotein receptor complex Important in Cell Biology?
The low-density lipoprotein receptor complex is critically important because it controls plasma cholesterol levels and mediates the uptake of LDL, a major risk factor for atherosclerosis. Dysregulation of this complex leads to hypercholesterolemia and cardiovascular disease, and it is also exploited by viruses for cell entry [5,7,8]. Furthermore, the complex participates in immune cell activation via mTORC1 signaling and in developmental pathways such as Wnt/beta-catenin signaling. Understanding its structure, assembly, and regulation is therefore essential for developing therapies for metabolic disorders, infections, and cancer.
• Maintains cholesterol homeostasis by mediating LDL uptake and degradation.
• Its dysfunction causes familial hypercholesterolemia and atherosclerosis.
• Serves as a receptor for multiple viruses, including yellow fever virus and Semliki Forest virus [5,7].
• Modulates immune responses through the LDLR-mTORC1 axis in CD8+ T cells.
• Participates in Wnt/beta-catenin signaling, influencing development and cancer.
• Is a target for PCSK9 inhibitors, which prevent LDLR degradation.
• Can bind xenobiotic toxins, affecting drug delivery and toxicity.
• Its recycling is regulated by SNX17, and disruption leads to receptor degradation.
• Structural knowledge of apoB100-LDLR interaction guides drug design.
• CRISPR models enable precise dissection of receptor function in health and disease [1,6].
What Happens During low-density lipoprotein receptor complex?
Ligand Binding and Receptor Activation
In simple terms: The receptor grabs LDL particles and other ligands on the cell surface.
The low-density lipoprotein receptor complex binds apolipoprotein B100 on LDL particles with high affinity, as revealed by the cryo-EM structure of the apoB100-LDLR complex. This binding is the first step in receptor-mediated endocytosis. The complex can also bind xenobiotic toxins and viral particles, such as yellow fever virus and Semliki Forest virus, through LDLR family members [5,7]. The interaction with VSV glycoprotein has been structurally characterized, showing how the receptor recognizes viral ligands.
Endocytosis and Endosomal Sorting
In simple terms: The receptor and its cargo are pulled into the cell and sorted in the endosome.
Upon ligand binding, the complex is internalized via clathrin-coated pits. In the endosome, the acidic environment causes the receptor to release its cargo, which is then degraded in lysosomes. The receptor itself is sorted for recycling back to the plasma membrane. PCSK9 binding to LDLR prevents SNX17-mediated recycling, leading to lysosomal degradation of the receptor.
Receptor Recycling
In simple terms: The receptor goes back to the cell surface to catch more LDL.
Recycling of the LDL receptor is essential for maintaining cellular cholesterol uptake. SNX17 facilitates the retrieval of LDLR from the endosome to the plasma membrane. Disruption of this recycling pathway by PCSK9 results in reduced surface LDLR levels and increased plasma cholesterol. The recycling process is a key regulatory node for therapeutic intervention.
Signal Transduction
In simple terms: The receptor can also send signals inside the cell.
The low-density lipoprotein receptor complex can act as a transducer of intracellular signal pathways. For example, the LDLR-mTORC1 axis coordinates CD8+ T cell activation, linking lipoprotein uptake to immune signaling. Additionally, LDLR family members such as LRP5/6 are involved in Wnt/beta-catenin signaling, which regulates gene expression during development and disease.
Key Genes Involved in GO:0062136 low-density lipoprotein receptor complex
The following genes encode proteins that are components or regulators of the low-density lipoprotein receptor complex and its related pathways.
| Gene | Major Role | Research Relevance |
|---|---|---|
| LDLR | Core receptor for LDL; binds apoB100 and mediates endocytosis | Central to cholesterol homeostasis; mutations cause familial hypercholesterolemia |
| APOB | Ligand for LDLR; apolipoprotein B100 on LDL particles | Structural studies of apoB100-LDLR complex |
| PCSK9 | Binds LDLR and promotes its degradation by preventing SNX17-mediated recycling | Therapeutic target for hypercholesterolemia |
| SNX17 | Facilitates LDLR recycling from endosomes to plasma membrane | Regulates receptor surface levels |
| VLDLR | LDLR family member; receptor for Semliki Forest virus | Viral entry and lipoprotein metabolism |
| LRP1 | Multifunctional receptor; binds multiple ligands | Signaling and clearance of proteases |
| LRP5 | Co-receptor for Wnt signaling | Development and cancer |
| LRP6 | Co-receptor for Wnt signaling | Development and cancer |
| MTOR | Kinase in mTORC1 complex; coordinates T cell activation with LDLR | Immune metabolism |
| MYD88 | Adaptor in TLR signaling; may cooperate with LDLR | Innate immunity |
| CD8A | T cell co-receptor; LDLR-mTORC1 axis in CD8+ T cells | Adaptive immunity |
| ARH | Adaptor protein for LDLR endocytosis | Familial hypercholesterolemia |
| DAB2 | Adaptor protein for LDLR endocytosis | Endocytic trafficking |
| IDOL | E3 ubiquitin ligase that promotes LDLR degradation | Regulation of cholesterol uptake |
| SREBF2 | Transcription factor regulating LDLR expression | Cholesterol homeostasis |
| HMGCR | Rate-limiting enzyme in cholesterol synthesis | Target of statins |
| NPC1L1 | Cholesterol uptake transporter | Intestinal cholesterol absorption |
How Is low-density lipoprotein receptor complex Regulated?
The low-density lipoprotein receptor complex is regulated at multiple levels. Transcriptionally, SREBP-2 controls LDLR expression in response to cellular cholesterol levels. Post-translationally, PCSK9 binds LDLR and promotes its degradation by preventing SNX17-mediated recycling. The inducible degrader of LDLR (IDOL) ubiquitinates LDLR and targets it for lysosomal degradation. Additionally, the LDLR-mTORC1 axis integrates nutrient and growth signals to coordinate CD8+ T cell activation. Wnt/beta-catenin signaling can also influence LDLR family member expression and function.
low-density lipoprotein receptor complex and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| LDLR | Familial hypercholesterolemia, atherosclerosis | LDLR knockout mice; CRISPR point mutation in LDLR ligand-binding domain |
| PCSK9 | Hypercholesterolemia | PCSK9 overexpression or knockout cell lines; SNX17 interaction studies |
| VLDLR | Semliki Forest virus entry | VLDLR knockout cells; viral infection assays |
| LRP5/6 | Wnt signaling in cancer and bone density | LRP5/6 knockout organoids; Wnt reporter assays |
| MTOR | T cell activation and autoimmunity | Conditional mTOR knockout in CD8+ T cells |
Atherosclerosis and Cardiovascular Disease
Dysfunction of the low-density lipoprotein receptor complex leads to elevated plasma LDL cholesterol, a major risk factor for atherosclerosis. Cross-organ metabolite production and consumption studies in atherogenic conditions highlight the systemic impact of LDLR dysfunction. Mutations in LDLR cause familial hypercholesterolemia, and PCSK9 gain-of-function mutations similarly reduce LDLR recycling.
Viral Infections
Multiple LDLR family members act as entry receptors for yellow fever virus, and VLDLR is a receptor for Semliki Forest virus [5,7]. The structural basis for VSV glycoprotein recognition of LDLR family members has been elucidated, providing insights into viral tropism and potential antiviral targets.
Immune Regulation and Cancer
The LDLR-mTORC1 axis coordinates CD8+ T cell activation, linking lipid metabolism to immune responses. Wnt/beta-catenin signaling, in which LRP5/6 are co-receptors, is frequently dysregulated in cancer. Thus, the complex influences both immune surveillance and tumorigenesis.
From low-density lipoprotein receptor complex-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does LDLR mediate LDL uptake? | LDLR knockout cell line (e.g., HepG2) with fluorescent LDL uptake assay |
| How does PCSK9 affect LDLR recycling? | PCSK9 overexpression and SNX17 knockout cells |
| What is the role of LDLR in T cell activation? | LDLR knockout CD8+ T cells with mTORC1 readouts |
| Can LDLR family members mediate viral entry? | VLDLR or LDLR knockout cells infected with yellow fever virus |
| What is the structural basis of apoB100 binding? | Recombinant LDLR ectodomain with apoB100 for cryo-EM |
| Does LRP6 cooperate with Wnt ligands? | LRP6 knock-in reporter cells; Wnt signaling assays |
How to Study the low-density lipoprotein receptor complex Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Cryo-EM | 3D structure of receptor-ligand complexes | ApoB100-LDLR structure |
| CRISPR knockout | Loss-of-function phenotypes | LDLR, PCSK9, SNX17 knockout cells |
| DiI-LDL uptake assay | LDL internalization and degradation | Cholesterol metabolism studies |
| Surface biotinylation | Receptor recycling and surface levels | PCSK9 and SNX17 regulation |
| Immunoblotting | Protein expression and phosphorylation | mTORC1 signaling |
| Luciferase reporter assay | Wnt/beta-catenin transcriptional activity | LRP5/6 function |
| Viral infection assay | Viral entry efficiency | Yellow fever virus and SFV entry [5,7] |
| Proteomics | Protein-protein interactions | Receptor complex composition |
Structural Biology (Cryo-EM and X-ray Crystallography)
The structure of apolipoprotein B100 bound to the LDL receptor was solved by cryo-EM, revealing the molecular details of ligand recognition. Similarly, the structure of Semliki Forest virus in complex with VLDLR and the VSV glycoprotein bound to LDLR family members have been determined [5,8]. These methods are essential for understanding the assembly and binding interfaces of the complex.
CRISPR-Cas9 Genome Editing
CRISPR knockout of LDLR, PCSK9, or SNX17 allows functional dissection of the receptor complex. For example, SNX17 knockout abolishes LDLR recycling, mimicking PCSK9-mediated degradation. Point mutations can be introduced to test specific residues in the ligand-binding domain of LDLR.
Endocytosis and Recycling Assays
Fluorescently labeled LDL (e.g., DiI-LDL) is used to measure uptake and degradation in wild-type and mutant cells. Receptor recycling can be assessed by surface biotinylation or antibody-feeding assays. These methods quantify the functional consequences of genetic perturbations.
Signaling Pathway Analysis
The LDLR-mTORC1 axis can be studied by immunoblotting for phospho-S6K and phospho-4E-BP1 in CD8+ T cells. Wnt/beta-catenin signaling is monitored using TOPFlash reporter assays in cells expressing LRP5/6 mutants.
How CRISPR Can Be Used to Study GO:0062136 low-density lipoprotein receptor complex
Knockout
CRISPR knockout of LDLR or its regulators (e.g., SNX17) is used to study loss-of-function phenotypes such as impaired LDL uptake and recycling. Knockout of VLDLR or LDLR family members can block viral entry, identifying essential receptors.
Point Mutation
Point mutations in the LDLR ligand-binding domain can mimic familial hypercholesterolemia mutations and test the importance of specific residues for apoB100 binding. Similarly, mutations in PCSK9 can be introduced to study gain-of-function effects on LDLR degradation.
Knock-in
Knock-in of tagged LDLR (e.g., GFP or HA) allows real-time imaging of receptor trafficking and recycling in live cells. Knock-in of disease-associated mutations in LRP5/6 can model Wnt signaling defects.
Overexpression
Overexpression of PCSK9 or IDOL in cell lines reduces surface LDLR levels, mimicking hypercholesterolemia conditions. Overexpression of LRP6 can enhance Wnt signaling and is used to study developmental pathways.
How EDITGENE Supports low-density lipoprotein receptor complex Research
Researchers studying low-density lipoprotein receptor complex-related genes often need to determine whether a candidate gene is causally involved in receptor assembly, trafficking, or signaling. EDITGENE provides a comprehensive suite of CRISPR services to enable precise genetic perturbations in relevant cell models.
Contact EDITGENE today to design your custom CRISPR model for low-density lipoprotein receptor complex research.
Frequently Asked Questions About low-density lipoprotein receptor complex
What is GO:0062136?
GO:0062136 is the Gene Ontology term for the low-density lipoprotein receptor complex, a plasma membrane protein complex with LDL particle receptor activity that can also bind xenobiotic toxins and mediate endocytosis.
What genes are involved in the low-density lipoprotein receptor complex?
Key genes include LDLR, APOB, PCSK9, SNX17, VLDLR, LRP1, LRP5, LRP6, and MTOR, among others [1,2,4,5,6].
Where is the low-density lipoprotein receptor complex located?
It is located at the plasma membrane, where it binds ligands and initiates endocytosis.
What is the function of the low-density lipoprotein receptor complex?
It mediates the uptake and degradation of LDL particles, recycles back to the plasma membrane, and can transduce intracellular signals.
How does PCSK9 regulate the low-density lipoprotein receptor complex?
PCSK9 binds LDLR and prevents SNX17-mediated recycling, leading to lysosomal degradation of the receptor.
Which viruses use the low-density lipoprotein receptor complex for entry?
Yellow fever virus, Semliki Forest virus, and vesicular stomatitis virus (VSV) can use LDLR family members as entry receptors [5,7,8].
What diseases are associated with the low-density lipoprotein receptor complex?
Atherosclerosis, familial hypercholesterolemia, viral infections, and cancer are associated with dysfunction of this complex [3,5,7].
How can CRISPR be used to study the low-density lipoprotein receptor complex?
CRISPR knockout, point mutation, knock-in, and overexpression models allow precise dissection of receptor function, trafficking, and signaling [1,6].
What is the role of the LDLR-mTORC1 axis?
It coordinates CD8+ T cell activation by linking lipoprotein receptor function to mTORC1 signaling.
What structural information is available for the low-density lipoprotein receptor complex?
The cryo-EM structure of apolipoprotein B100 bound to LDLR provides high-resolution details of the ligand-receptor interaction.
Conclusion
The low-density lipoprotein receptor complex (GO:0062136) is a multifunctional plasma membrane machine that controls cholesterol uptake, participates in signal transduction, and serves as a portal for viral entry. Its dysfunction underlies major human diseases, including atherosclerosis and infections. Advances in structural biology and CRISPR genome editing are illuminating its assembly, regulation, and therapeutic potential. EDITGENE offers comprehensive CRISPR services to accelerate research on this complex and its associated genes.
References
- 1. Reimund M et al.. 2025. Structure of apolipoprotein B100 bound to the low-density lipoprotein receptor.. Nature 638(8051):829-835 PMID: 39663455
- 2. MacDonald BT et al.. 2009. Wnt/beta-catenin signaling: components, mechanisms, and diseases.. Dev Cell 17(1):9-26 PMID: 19619488
- 3. Bae H et al.. 2025. Cross-organ metabolite production and consumption in healthy and atherogenic conditions.. Cell 188(16):4441-4455.e16 PMID: 40436017
- 4. Bonacina F et al.. 2022. The low-density lipoprotein receptor-mTORC1 axis coordinates CD8+ T cell activation.. J Cell Biol 221(11) PMID: 36129440
- 5. Cao D et al.. 2023. Structure of Semliki Forest virus in complex with its receptor VLDLR.. Cell 186(10):2208-2218.e15 PMID: 37098345
- 6. Guan Y et al.. 2025. PCSK9 Promotes LDLR Degradation by Preventing SNX17-Mediated LDLR Recycling.. Circulation 151(21):1512-1526 PMID: 40071387
- 7. Chong Z et al.. 2026. Multiple LDLR family members act as entry receptors for yellow fever virus.. Nature 649(8095):173-182 PMID: 41162706
- 8. Nikolic J et al.. 2018. Structural basis for the recognition of LDL-receptor family members by VSV glycoprotein.. Nat Commun 9(1):1029 PMID: 29531262
