Highly Selective Fluorescent Biosensor for Labeling His-Tagged Proteins in a Specific Conformation

A rapid, label-free biosensor for detecting specific conformation of His-tag labeled proteins, accessible for use in both academic- and commercial-R&D. The fluorescent biosensor detects and labels His-tagged proteins in complex environments, such as living cells, while offering high sensitivity, speed, and cost-effectiveness.

Fluorescent biosensing has become a valuable tool in analytical research, while at the same time the poly-histidine tag (His-tag) has become the most commonly used tag for protein labeling.  However, commercial products for labeling and detecting conformational changes in His-labeled proteins suffer from three main limitations: First is their inability to identify specific changes in the protein conformation. Second, even if such changes are detected, labeling of His-tag proteins is usually very laborious. And third, commercial probes tend to be large and consequently can interfere with the proteins function.  Therefore, there is a need for a small, direct, and non-interfering fluorescent probe for detection of conformational changes.

Dr. Margulies and his team have developed a first of its kind fluorescent molecule that provides detection of changes to the surface of His-labeled proteins. Subsequently, labeling proteins only if they are in a specific conformation. The biosensor exhibits high affinity, excellent signal-to-noise ratio and can be easily applied with no fixation or tedious protocols.

Using the technology, many proteins and specific conformations can now be labeled and studied for the first time (proteins that were already successfully labeled using the biosensor: Calmodulin, B-cell lymphoma 2, G-protein).