Membrane Protein Technology Platforms
Multipass transmembrane proteins play essential roles in cell growth, signal transduction, and intercellular communication, extensively involved in various physiological processes. They are also important targets for drug discovery and development. However, producing soluble recombinant forms of these proteins has long been a significant challenge, impeding the progress of new drug discovery.
We have developed two transmembrane protein display platforms: virus-like particles (VLPs) and nanodiscs, designed for robust, functional display of full-length, multipass- transmembrane proteins in their native conformation. Our platform technology preserves the structural integrity and biological activity of the membrane proteins, enabling a broad range of applications, including immunization, antibody screening, analytical assays such as SPR, BLI and ELISA. Our transmembrane protein products undergo strict bioactivity and purity testing using SPR, ELISA, flow cytometry, and HPLC, ensuring outstanding functional performance and high batch consistency for reproducible results.
Virus-like Particle (VLP)
Virus-like particles (VLPs) are non-infectious nanoscale structures that closely mimic the organization and shape of native viruses but lack viral genetic material. They comprise self-assembled viral structural proteins and are highly immunogenic due to their repetitive, multivalent surface.
How the VLP displays transmembrane proteins.
Advantages of displaying membrane proteins on VLPs
Native-like Conformation: VLPs provide a lipid bilayer environment that helps transmembrane proteins maintain their correct folding, topology, and conformation, closely mimicking their native state on the cell membrane.
Enhanced Immunogenicity: The repetitive, multivalent display of antigens on VLPs significantly boosts immune responses compared to soluble or monomeric proteins, making them ideal for vaccine and antibody development.
Stabilization of Difficult Targets: Transmembrane proteins are often unstable or insoluble when isolated. VLPs offer structural support, increasing protein stability and solubility during purification and immunization.
Improved Antibody Generation: Presenting transmembrane proteins on VLPs enhances the likelihood of generating antibodies against conformational epitopes, which are often lost in linear peptide or denatured formats.
No Genetic Material = High Safety: VLPs are non-infectious because they lack viral genetic material, offering a safe platform for research and therapeutic development.
Product Features:
→ Mammalian cell expression system for natural folding and glycosylation
→ Strong Immunogenicity
→ Validated biological activity via ELISA and SPR
→ High batch-to-batch consistency
→ Site-specific biotinylation available
Applications:
→ Immunization
→ Antibody Screening
→ Analytical Assay Method Development and Testing
→ PK/PD studies
Product Validation
Claudin 18.2 is a tetraspanin protein family member of critical therapeutic potential for gastric and esophageal adenocarcinomas. Despite interest in drug development targeting Claudin 18.2, technical challenges in expressing high-quality Claudin 18.2 protein have significantly limited the progress of Claudin 18.2-targeted drug discovery and development. By leveraging virus-like particles, we have become the first company to successfully produce the commercially available, full-length human Claudin 18.2 protein in soluble format. Our consistent activity and purity testing results demonstrate the functional integrity and bioactivity of our VLP-displayed
protein platform.
Figure 1. Intensity distribution of Claudin 18.2 VLPs measured by dynamic light scattering (DLS). The peak centered at approximately 150 nm indicates a homogeneous VLP particle size.
Figure 2. The chromatogram shows the high-performance liquid chromatography (HPLC) profile of Claudin 18.2 VLPs, with a prominent peak observed at 4.909 minutes, indicating the retention time of the Claudin 18.2 protein. The sharp and well-defined peak suggests a high purity and consistency of the VLP preparation.
Figure 3. Immobilized Human Claudin 18.2 VLPs at 5ug/ml (100 ul/Well) on the plate. Dose response curve for Anti-Claudin 18.2 Antibody, hFc Tag with the EC50 of 6.6, 7.4, 8.3,7.3 ng/ml determined by ELISA.
Figure 4. Biotinylated Claudin 18.2 VLPs captured on CM5 Chip via Streptavidin can bind Anti-Claudin18.2 Antibody with an affinity constant of 1.28 nM as determined in SPR assay (Biacore T200).
Nanodiscs are membrane-mimetic structures composed of a phospholipid bilayer and membrane scaffold proteins. They serve as important tools for stably displaying multi-pass transmembrane proteins with native conformation and protein activity. At KACTUS, we leverage a detergent-free production process to produce SMA-based nanodiscs as our catalog products to maximally maintain the native structure and conformation of the full-length, multi-pass transmembrane proteins in soluble format, allowing wide applications in drug screening, analytical assay development and testing.
Structure & Expression
Full-length multi-pass transmembrane proteins are expressed in HEK293 cells. Copolymers interact with the membrane to form a disc-like structure around the target protein. The cellular phospholipids are retained, creating a stable nanodisc that mimics the natural membrane environment. This approach avoids the pitfalls of detergent extraction and streamlines the production process.
Advantages of displaying membrane proteins on SMA-Based Nanodisc
Detergent-Free Solubilization: SMA polymers solubilize membrane proteins directly from membranes without detergents, preserving delicate protein-lipid and protein-protein interactions.
Native Lipid Environment: Unlike synthetic nanodiscs (e.g., MSP-based), SMA nanodiscs contain endogenous lipids, which can be essential for structural integrity, function, and drug binding.
Better Protein Stability: Many membrane proteins remain more stable and active in SMA nanodiscs than in detergent micelles.
Broad Applicability: Effective for solubilizing a wide range of membrane proteins, including GPCRs, ion channels, and transporters.
Product Features
→ Mammalian cell expression system for natural folding and glycosylation
→ Detergent-free, natural phospholipid environment
→ Validated biological activity via ELISA and SPR
→ High batch-to-batch consistency
→ Site-specific biotinylation available
Applications
→ Antibody Panning
→ Antibody Screening
→ Analytical Assay Method Development and Testing
→ PK/PD studies
Product Validation
GPRC5D Nanodisc
GPRC5D is a G protein-coupled receptor (GPCR) with 7-transmembrane domains. It is a popular target for relapsed/refractory multiple myeloma. This protein is being explored as a targeted in CAR-T cell therapy, and bispecific antibody drugs (with CD3 protein) for myeloma. To facilitate GPRC5D drug development, we have developed the full-length GPRC5D nanodisc with verified bioactivity through ELISA, BLI and SPR.
Figure 7. ELISA data demonstrates Human GPRC5D Nanodisc can bind to Anti-GPRC5D antibody with an EC50 of 4.9ng/mL.
Figure 8. Human CD3E&CD3D was immobilized on the plate, followed by Anti-Human CD3×GPRC5D Bispecific Antibody binding, followed by Biotinylated Human GPRC5D Nanodisc. Results demonstrate quality performance in ELISA to of the nanodisc to Anti-Human CD3×GPRC5D bispecific antibody with an EC50 of 0.28 μg/mL.
Figure 9. BLI data demonstrates Biotinylated Human GPRC5D Nanodisc can bind to Anti-GPRC5D Antibody with high affinity (KD=1.16nM).
Figure 10. SPR data demonstrates Human GPRC5D Nanodisc can bind to Anti-GPRC5D Antibody with a high affinity (KD = 1.47nm).
Available Products
Frequently Asked Questions
Generally, VLPs range in size from approximately 100 to 200 nm. The size of nanodiscs is typically less then 20 nm.
Our VLPs are produced with high quality standards. Although it is difficult to determine the exact number of copies of the antigen displayed on the surface of the VLP, we take steps to validate each batch of VLPs to assure the displayed protein will have consistency across batches.
For VLPs, the biotins are introduced into the VLP independent to the target protein. Therefore, it will NOT interfere with the structure and surface epitope of target membrane proteins.
For Nanodiscs, the biotin is located at the C-terminus of the membrane proteins.
To guarantee transmembrane protein quality, KACTUS follows a strict validation process involving various analytical techniques for each batch. QC data usually includes HPLC, ELISA, and SPR.
Yes! Please feel free to contact us here to request a custom VLP protein service.
Our SMA-based nanodiscs are not recommended for animal immunization. The SMA is a copolymer that animals may not be able to tolerate after immunization.
Contact us to request more information or set up a meeting with one of our team members.
Related Products & Information
Membrane Protein Products & Services
60 Hickory Drive
Waltham, MA 02451
United States
Multipass Transmembrane Proteins Display Platforms | VLPs & Nanodisc Proteins | KACTUS