Cell biologists have the difficult job of singling out the impact an individual protein within a cell packed with thousands of proteins. One way to distinguish the function of a protein is to turn it on or off and study the effect it has on a cell. For decades, researchers have been assembling a toolbox of techniques to do just that. But so far, these tools have been limited in their ability to reversibly turn proteins on and back off again.
A recent approach published in the journal eLife uses blue light to give researchers greater control over when and where a protein is activated. The new tool, which the researchers have dubbed "LightR", is shaped like a clamshell made of parts of two photoreceptor proteins from the fungus Neurospora crassa, a red bread mold.
The researchers engineered the LightR clamshell into the active site of Src, the protein they were interested in switching on and off. In the dark, the clamshell is “open” and pulls the Src active site into an inactive state. The introduction of blue light causes the clamshell to snap closed, restoring the original shape of the Src active site and turning on the protein. When they tested this system in cells, they were able to turn on Src activity with blue light and then turn the protein activity back off by putting the cells in the dark.
With careful protein engineering, researchers around the world could add LightR to their toolboxes. The ability to control when a protein is turned on and off brings protein studies out of the dark and into the light.