A standardized route to broader
Membrane Protein Screening & Purification


Start with 2 standardized screens & scale effortless
up to 6 - optimized for your workflow

Membrane protein purification should be easy!

But in practice, membrane proteins require special attention, especially if you need to preserve native protein properties for downstream assays.

Top 3 bottlenecks in membrane protein purification

Manual handling

  • Protocols are long
  • It's error-prone and can be user-dependent
  • Purifying many samples manually is not scalable

Optimising conditions

  • Each protein behaves differently
  • Ideal conditions cannot be predicted - screening is essential
  • This adds time and complexity to the purification stage of a project

Preserving native
protein behaviour

  • Solubilisation and stabilisation agents are key for native protein prep
  • Traditional protocols remove native lipid environment with detergents
  • Identifying best solubilisation agent takes time

Get the KingFisher™ Flex Screening & Purification Protocol

NativeMP™ Screening & Purification Plates made to scale

NativeMP™ Screening & Purification plates are a ready-to-run product, designed for use with KingFisher™ Flex. The workflow combines two experimental processes in a single run:

Screening

for optimal solubilisation tools that preserve native protein properties.

Purification

of membrane proteins that deliver analytical-grade proteins in just 90 minutes instead of 20 hours.

3 Components - One Automated Workflow

For membrane protein screening to purification you just need 3 components

1. NativeMP™ Screening Plate: Preloaded with 16 selected copolymers

2. NativeMP™ Purification Plates: Choose your affinity MagBeads

a.) Rho1D4 MagBeads Rho1D4 Protocol

b.) Strep-Tactin®XT MagBeads Strep-Tactin®XT Protocol

c.) Anti-DYKDDDDK MagBeads Anti-DYKDDDDK Protocol

How does the NativeMP™ Screening & Purification Plate workflow operate?

  1. Prepare your cell lysate
    - Lyse your cells using your method of choice
    - Centrifuge at 9,000 x g for 45 minutes
    - Collect the supernatant

  2. Load the sample
    - Transfer the supernatant into the NativeMP™ Screening Plate containing copolymers

  3. Prepare the purification plates
    - Resuspend the MagBeads from the NativeMP™ Purification Plate
    - Prepare three plates with identical loading schemes using wash buffer
    - Prepare one additional plate with elution buffer

  4. Run the automated purification
    - Load all plates into the KingFisher system
    - Start the programmed workflow

  5. Collect your protein
    - After approximately 90 minutes, collect your stabilized and purified membrane protein

Parallel Membrane Protein Screening on KingFisher – made to scale 

Your Set targeted to your preferred Tag or choose single Plates – whatever suits your Research

Save Time & Focus on Results.

Get from cell suspension to analytical-grade membrane proteins with ready-to-run plates in 90 min instead of 20 h

  • 20× higher yield in just 90 minutes
  • Parallel screening of 2, 4 or 6 targets in a single run 
  • Flexible purification tailored to your tag 
  • Scalable workflow with built-in reproducibility

Why NativeMP™ Screening & Purification Plates?


From screening to purification - in one seamless system
​ Eliminate workflow breaks and streamline your membrane protein pipeline from start to finish.​ ​

Reproducible, scalable, and efficient​
Generate consistent results across experiments while easily scaling from small screens to larger studies.​ ​

Standardized condition screening
​ Reduce variability with a controlled, plate-based format designed for reliable and comparable results.

​ ​ Flexible purification tailored to your tag​
Adapt purification strategies to your specific affinity tag without changing the overall workflow.​ ​

Fully automated processing
​ Minimize hands-on time and obtain highly pure membrane proteins directly usable for Cryo-EM and analytical analysis. 

NativeMP™ and PlateX MP™ FAQ

How much copolymer do I need to add to each buffer after solubilization?
None. Once stable, copolymer nanodiscs do no need any additional copolymer to remain stable. They are not detergent micelles that need resupply to stay intact.
What amount of cells do I need to add into the wells of the plates?
Resuspend the cell pellet in 5 ml of protein buffer (HEPES) per gram of pellet. Add 1.8–2 ml of this resuspension to each corresponding well on the plate. Note: When working with the KingFisher Plates it is only 1ml.
My membrane protein constructs carry the His-tag, do you also have these magnetic beads for His-tagged proteins?
We indeed offer PureHT Plates carrying Ni-INDIGO-MagBeads (90300). But these do not include copolymers PureHT is purely for protein purification in Systems like the KingFisher™.

We generally recommend against the His-tag when it comes to membrane proteins. It may generate the most yield, but it is comparatively low on purity, especially when compared to Rho1D4 or the Twin-Step-Tag. And with membrane proteins having a lower abundance than their soluble counterparts, it is better to use high-purity tags instead of high-yield ones.
The protein I am working with was previously solubilized with a copolymer that is not included in these plates. Why?
We chose 16 copolymers representing both old and new generations. Here, we focused on the copolymers which have shown better results for membrane proteins in general over the last years. This should allow for a better comparison between generations and also give us a broad overview of which copolymers are better suited for which type of membrane protein.
How is NativeMP™ different to SMALP?
SMALP is short for SMA-Lipid-Particle and it was the first commercially available copolymer for nanodisc creation. In short SMALPs are included in the NativeMP system. They are not something different. NativeMP™ just includes additional copolymer backbones than SMA and therefore the term SMALP would have been limiting and misleading to use.
What type of cells can I use with NativeMP™ ?
All cell types without a cell wall can be directly lysed and centrifuged at 9,000 g, and the supernatant can be directly used. For cells with a cell wall, the cell wall must first be removed, followed by cell lysis and centrifugation.
What type of sample can be used for NativeMP™ treatment? / How do I need to prepare my cells in before they come into contact with NativeMP™?
In-house, Cube Biotech typically sonicates cells before adding the copolymer to the suspension. Starting from a pure cell pellet is also possible, though this may result in lower yields. Older protocols required separating the membrane fraction from a cell lysate by ultracentrifugation prior to NativeMP™ treatment. This is beneficial to do to remove cell debris before copolymer treatment, but it is no longer necessary, as the improved performance of next-generation copolymers.
What expression scales are typical for solubilizing with these polymer-based nanodiscs?
In-house, we routinely work with 300 ml of cell culture volume per pellet. After harvesting, the pellet is resuspended, lysed, and centrifuged, and the resulting supernatant is split into aliquots for individual wells on the PlateX MP plates.
What are the current protocols for running polymer-purified protein on SDS-PAGE? Is polymer removal still recommended? Or Polymer-specific?
At Cube Biotech we only heat or SDS samples at 46°C for 30 min. Orogen does not heat their samples but uses them right away. We do not remove the copolymer before SDS-PAGE.
At what temperature must I do the copolymer treatment? Do I have to move my automation hardware to the cold-room?
Copolymer based solubilization, compared to many detergent-based approaches, is done at room temperature. Another advantage of NativeMP. In non-automated approaches we even recommend sometimes to increase the treatment temperature to 37°C for better solubilization rates, but this is not always necessary.
The wash buffers that I am using contain a small concentration of detergent (e.g. 0.1% Tween). Can NativeMP™ nanodiscs withstand that?
If your protein buffers require detergents, it is critical to keep the detergent concentration below the Critical Micelle Concentration (CMC) of that detergent. Exceeding the CMC will cause the copolymer nanodiscs to dissolve and be replaced by conventional detergent micelles.
Are these single-use plates?
Yes. After use, the buffers are used up, and the copolymers are used up. Only the MagBeads could in theory be regenerated.
What assays can be run to characterize copolymer-stabilized proteins?
The whole idea behind copolymer nanodiscs is to provide the membrane protein with an environment that preserves the native conformation—something that is not guaranteed and is often impaired when using detergents.
Our standard in-house procedure is to check protein/nanodisc integrity with DLS, NanoDSF, Coomassie staining, and Western blot.
Furthermore, copolymer-nanodisc-stabilized membrane proteins are perfectly suited for structure determination using cryo-EM. Structures we determined during test runs were equivalent to previously confirmed data—a definitive sign that the native conformation is maintained.
Does NativeMP™ keep membrane protein complexes together or only solubilized individual membrane proteins?
NativeMP™ is capable of keeping membrane protein complexes intact.

NativeMP™ Screening & Purification Plate Portfolio