LDLR

Background

The LDLR gene is located in the 19p13.2 region of the human chromosome and encodes the low-density lipoprotein receptor (LDLR), a member of the LDL receptor family of cell surface receptors. LDLR is a single-pass type I transmembrane glycoprotein, organized into five functional regions: an N-terminal ligand-binding domain containing seven cysteine-rich LDL-A repeats that coordinate calcium ions, an EGF-precursor homology domain with a six-bladed β-propeller, a serine/threonine-rich O-linked glycosylation region, a single transmembrane helix, and a cytoplasmic tail bearing an NPXY motif for clathrin-mediated internalization. Its molecular weight is approximately 95 kDa and it is expressed across virtually all cell types, with the liver accounting for roughly 70% of the total body LDLR pool. As the primary mechanism for clearing low-density lipoprotein from the circulation, LDLR binds apolipoprotein B-100 on LDL particles at the plasma membrane at neutral pH, undergoes clathrin-mediated endocytosis, and releases the bound lipoprotein in acidic endosomes through a pH-dependent conformational switch involving the β-propeller domain. The receptor then recycles to the cell surface while LDL is delivered to lysosomes for cholesterol release. This process plays a central role in maintaining cellular and systemic cholesterol homeostasis. LDLR expression is transcriptionally regulated by the SREBP pathway in response to intracellular cholesterol levels, and post-translationally modulated by PCSK9, which binds the receptor and redirects it toward lysosomal degradation instead of recycling. The LDLR gene is highly polymorphic, with numerous genetic variants distributed across all 18 exons that can affect receptor synthesis, ligand binding, internalization, or recycling. Therefore, LDLR is regarded as a fundamental molecular model for studying receptor-mediated endocytosis and cholesterol metabolism. Its functional analysis provides valuable tools for understanding the regulatory mechanisms of lipid transport, the structure-function relationships of modular receptor proteins, and the molecular basis of genetic variation affecting receptor activity.

Fig. 1 A schematic presentation of full-length LDLR and its truncated mutants that lack the ligand binding domain (∆LBD) and epidermal growth factor like domain (∆EGF).¹

Function of LDLR Protein: A Key Endocytic Receptor Driving Cellular Cholesterol Homeostasis

The functional spectrum of LDLR encompasses multiple layers of regulatory activity in cholesterol metabolism and is continuously being elucidated:

• Ligand recognition and receptor-mediated endocytosis: LDLR binds apolipoprotein B-100 on LDL particles and apolipoprotein E on VLDL and IDL particles through its N-terminal ligand-binding domain, which comprises seven LDL-A repeats that require calcium ions for structural integrity and ligand recognition. Upon ligand engagement at the cell surface, the NPXY motif in the cytoplasmic tail interacts with clathrin adaptor proteins including DAB2 and LDLRAP1, directing the receptor-ligand complex into clathrin-coated pits for rapid internalization.
• pH-dependent ligand release and receptor recycling: Following internalization, the acidic environment of the endosome triggers a conformational rearrangement in the EGF-precursor homology domain: the β-propeller contacts repeats 4 and 5 of the ligand-binding domain, displacing the bound lipoprotein. The receptor then returns to the plasma membrane via recycling endosomes while the released lipoprotein is trafficked to lysosomes for degradation and cholesterol liberation. This pH-sensitive switch ensures efficient cargo release and receptor reuse.
• Transcriptional and post-translational regulation: LDLR expression is under tight feedback control through the SREBP pathway: when intracellular cholesterol is abundant, SREBP processing is suppressed, reducing LDLR transcription; conversely, cholesterol depletion activates SREBP and upregulates LDLR synthesis. At the post-translational level, PCSK9 binds to the EGF-A domain of LDLR and redirects the internalized receptor from the recycling pathway to lysosomal degradation, providing an additional layer of regulatory control over cell-surface LDLR abundance.
• Structure-function relationships and genetic variation: The modular architecture of LDLR connects discrete structural domains to specific functional properties. Variations in the ligand-binding domain can alter lipoprotein recognition, while mutations in the EGF-precursor homology domain may impair pH-dependent ligand release. Changes in the cytoplasmic tail can affect internalization kinetics. Elucidating how sequence variation at each structural module affects receptor trafficking, ligand binding, and recycling efficiency provides insights into the molecular logic governing receptor-mediated endocytosis and cholesterol transport.

LDLR Membrane Protein Product

Creative Biolabs offers a comprehensive series of high-quality LDLR membrane protein products designed to support structural and functional investigations of receptor-mediated endocytosis and cholesterol metabolism. Built upon the independently developed MemDX™ recombinant membrane protein technology platform, LDLR proteins can be prepared through multiple expression systems, including virus-like particles (VLP) and in vitro prokaryotic expression systems, among others. These rigorously characterized protein products, which include MemDX™ recombinant human LDLR membrane protein (as virus-like particles) and human LDLR proteins derived from diverse expression systems, are suitable for ELISA, antibody screening and identification, ligand binding experiments, and functional research, equipping investigators with dependable reagents for analyzing LDLR-mediated lipoprotein recognition and endocytic trafficking mechanisms.

LDLR Protein Product

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LDLR Stable Cell Line Product

Constructing a robust cell model is crucial for investigating LDLR function in receptor-mediated endocytosis and cholesterol uptake. As a plasma membrane receptor that undergoes constitutive clathrin-mediated internalization and recycling, the cell-surface abundance and trafficking kinetics of LDLR directly determine the efficiency of lipoprotein clearance and cellular cholesterol acquisition. Alterations in LDLR expression, ligand-binding capacity, or recycling efficiency may lead to significant changes in cellular lipid homeostasis. Creative Biolabs offers customized LDLR membrane protein stable transfection cell models, covering wild-type and various functionally characterized forms. These models stably express the target protein on the plasma membrane, and are suitable for studies on fluorescent LDL uptake assays, receptor trafficking and recycling kinetics, ligand-binding measurements, and quantitative assessment of cholesterol regulatory pathways, providing a reliable and reproducible platform for exploring the molecular mechanism, structure-function relationship, and regulatory role of LDLR in cholesterol metabolism. Our technology ensures correct protein localization and plasma membrane integrity, facilitating your research.

LDLR Stable Cell Line Product

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LDLR Recombinant Antibody Product

Creative Biolabs offers highly specific recombinant antibodies targeting LDLR, produced using advanced recombinant antibody technology. Compared to traditional antibodies, these recombinant antibodies demonstrate superior performance in terms of specificity, sensitivity, and batch-to-batch consistency. They can also be modified and labeled in various ways. Our LDLR recombinant antibodies support a wide range of applications, including Western Blot, ELISA, flow cytometry, immunofluorescence, immunocytochemistry, immunohistochemistry, and immunoprecipitation, and can be used to detect differences in LDLR expression levels in various tissues or cell sources, analyze its plasma membrane localization and intracellular trafficking patterns, and conduct related research such as lipoprotein binding analysis and endocytic pathway investigation. These antibodies provide reliable detection tools for the structural analysis, functional study of LDLR, and the investigation of its role in receptor-mediated endocytosis and cholesterol homeostasis.

LDLR Recombinant Antibody Product

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Product Features

• Multiple expression platforms: Recombinant proteins can be produced through several expression systems (encompassing virus-like particles and both prokaryotic and eukaryotic hosts), addressing the requirements of diverse experimental settings.
• Broad experimental compatibility: The products are suitable for use in ELISA, antibody screening, binding assays, Western Blot, immunofluorescence, immunohistochemistry, and related applications.
• Consistent quality across batches: Strict quality control measures maintain product uniformity between batches, ensuring experimental results remain reproducible and dependable.
• Tailored customization services: Personalized services are available for specific protein forms, labeling approaches, or preferred expression platforms.

Custom LDLR Membrane Protein and Antibody Discovery Services

In addition to the standard products, Creative Biolabs also offers professional customized services for LDLR. LDLR is a modular multi-domain receptor whose distinct structural regions mediate ligand binding, pH-dependent conformational switching, and intracellular trafficking. These structural features present specific requirements in aspects such as membrane protein expression, antigen design, and functional characterization. Leveraging our technology platform, we can assist you in completing the following customized projects:

• Customized production of plasma membrane receptors: Tailored expression (using multiple expression systems), purification, and characterization for full-length LDLR and its individual functional domains including the ligand-binding region and EGF-precursor homology domain.
• Customized antibody development: From antigen design to antibody engineering (monoclonal, polyclonal, recombinant antibodies), supporting domain-specific detection or common epitope recognition across LDLR family members.
• Construction of stable cell models: Generate stable cell models expressing wild-type or functionally modified LDLR, suitable for lipoprotein uptake and receptor trafficking studies.
• Development of functional detection systems: Design and execute experimental protocols such as fluorescent LDL uptake assays, pH-dependent ligand release measurements, and quantitative assessment of receptor recycling kinetics.

Frequently Asked Questions (FAQ)

1. What is the main function of the LDLR protein?

   LDLR functions as the primary cell-surface receptor for clearing low-density lipoprotein from the circulation through receptor-mediated endocytosis. Its N-terminal ligand-binding domain recognizes apolipoprotein B-100 on LDL particles at neutral pH, and its cytoplasmic NPXY motif directs the receptor-ligand complex into clathrin-coated pits for internalization. In the acidic environment of endosomes, a pH-dependent conformational change in the β-propeller domain displaces the bound lipoprotein, allowing LDLR to recycle to the cell surface while LDL is delivered to lysosomes for cholesterol release. LDLR serves as a fundamental model for studying receptor-mediated endocytosis, modular protein architecture, and cholesterol homeostatic regulation.

2. Why is LDLR an important research target?

   LDLR possesses a well-characterized modular domain architecture in which discrete structural regions mediate ligand recognition, pH-responsive conformational switching, and intracellular trafficking. Investigating LDLR provides insights into the molecular mechanisms of clathrin-mediated endocytosis, the structural basis of ligand-receptor interactions, and the regulatory networks controlling cholesterol metabolism including the SREBP transcriptional pathway and PCSK9-mediated post-translational regulation. The receptor's central role in lipoprotein clearance and its highly polymorphic nature make it a valuable system for studying the relationship between protein structure, trafficking dynamics, and cellular lipid homeostasis.

3. Is the LDLR product of Creative Biolabs suitable for clinical applications?

   Not applicable. All LDLR products and services provided by Creative Biolabs are for research purposes only and cannot be used for any clinical diagnosis, prevention, treatment or cure of any disease.

4. What types of LDLR products does Creative Biolabs offer?

   We offer a variety of product types, including recombinant LDLR membrane proteins, stable cell models expressing LDLR, high-quality recombinant LDLR antibodies, as well as comprehensive customized services.