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Watching proteins dance

Proteins are so small that visualising them working in a cell has long been elusive, but a new study, published in Cell, has found a way to ‘film’ how they move.

These tiny molecules, which include insulin, haemoglobin and collagen, do all sorts of things to run our bodies, carrying out work in our cells to keep us alive. Researchers overcame the difficulty of visualising them by developing a new technique called ‘binder-tag’ that tracks active proteins in real time.

“No one has been able to develop a method that can do, in such a generalisable way, what this method does,” says study co-senior author Klaus Hahn, of the University of North Carolina School of Medicine. “So I think it could have a very big impact.”

Individual molecules followed within live cells. When they change color, they have adopted a new conformation, something Scientists could not previously see or study.

The technique involves two parts: a fluorescent binder and a molecular tag that is attached to the proteins of interest.

When inactive, the tag is hidden inside the protein, but when the protein is ready for action it changes shape and exposes the tag.

The binder then joins to the exposed tag and fluoresces. This new fluorescence can easily be tracked within the cell. 

Nothing else in the cell can bind to the binder or tag, so they only light up together on the active protein.

This type of visualisation will help researchers understand the dynamics of a protein in a cell.

“For a lot of protein-related diseases, scientists haven’t been able to understand why proteins start to do the wrong thing,” says Hahn. “The tools for obtaining that understanding just haven’t been available.

“With this method we can see, for example, how microenvironmental differences across a cell affect, often profoundly, what a protein is doing.”