Membrane protein interactions

What is the biological relevance of membrane protein interactions?

Overview of membrane proteins

Membrane protein interactions are crucial to a multitude of biological processes including:

Cellular communication – membrane proteins can function as transmembrane receptors. When ligands bind these receptors transmit extracellular signals intracellularly. This process is crucial in:
- Signal transduction
- Immune responses
- Hormonal regulation

The transport of molecules - membrane proteins can also act as ion channels, or transporters. This allows the movement of charged or bulky molecules across the cell membrane. Some examples are:
- Facilitating ions movement while maintaining cell membrane potential
- Drug transport, particularly of bulky compounds
- Active transport of substances against their concentration gradient from an area of low concentration to an area of high concentration

Importance of membrane proteins in drug discovery

Membrane protein interactions have significant impacts on health and disease and are key pharmaceutical drug targets.

Around 30% of all prescription pharmaceuticals on the market target G protein-coupled receptors (GPCRs). Because of their cellular function, they are interesting drug targets. However, their complex structure and hydrophobic areas make that they are also notoriously hard to study.

Introducing WAVEsystem: your ally in membrane protein kinetic analysis

WAVEsystem is a cutting-edge device which facilitates the study of biomolecular interactions between membrane proteins and proteins, small molecules or fragments. These interactions are notoriously difficult to analyze due to the instability of the membrane proteins outside of their native cell membrane environments.

WAVEsystem utilizes Grating Coupled Interferometry (GCI) technology, a highly sensitive, label-free technique that enables real-time monitoring of molecular interactions, including binding kinetics and affinities.

Also supported by:

Robust microfluidics - ensures membrane protein interaction analysis under near-native conditions
High sensitivity - screen interactions against complex targets, even at low-abundance
waveRAPID kinetics- swiftly analyse fragile proteins without compromising data quality

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WAVEsystem

Challenges of membrane protein interaction analysis

The binding affinity and interaction kinetics of membrane proteins – particularly GPCRs are notoriously difficult to study. When GPCRs are extracted from a cell membrane, their high hydrophobicity leads to rapid disassembly, rendering the sample useless for analysis.

How the WAVEsystem can help

When removed from their native environment, GPCRs deteriorate quickly – WAVEsystem, WAVEchips and waveRAPID provide a triple solution.

Assays can be rapidly optimized with WAVEsystem to select the optimal protein construct.

Utilizing all four sensor surfaces, testing a series of constructs against control compounds allows for the identification of optimal constructs and conditions with the highest chances of producing a robust screening assay to pursue further with structural studies.

Crude sample compatibility saving time with less purification steps.

WAVEchips and the no-clog microfluidics allow the use of crude samples, such as membrane preparations, reducing time needed for purification and ensuring no downtime from instrument clogging.

Screening can be done in hours rather than days with waveRAPID.

Researchers can screen more analytes using waveRAPID compared to traditional biosensor-based methods – as a result the membrane protein sensor surface will remain active during the whole screening assay.
Even if activity is decreasing, best-in-class sensitivity means even low signals or weak interactions are detected and analysed!