Rare blue proteins from cold-adapted microbes can serve as prototypes to design molecular on-off switches for cells, according to a new study from the European Molecular Biology Laboratory.
In the frozen reaches of our planet, the glaciers, mountaintops, and icy groundwater, significant research has been taking place. As an example of one research stream, scientists have uncovered strange light-sensitive molecules in tiny microbes. These “cryorhodopsins” can respond to light in ways that might let researchers turn brain cells on and off like switches.
Rhodopsins (visual purple, is a protein encoded by the RHO gene) have already been modified to serve as light-operated switches for electrical activity in cells. This technique, called optogenetics, is used by neuroscientists to selectively control neuronal activity during experiments. Rhodopsins with other abilities, such as enzymatic activity, could be used to control chemical reactions with light, for example.
Glowing under UV
Microbial rhodopsins are omnipresent on Earth, however the vast majority of them remain uncharacterized.
Some of these molecules can glow blue, a rare and useful trait for medical applications. Hence, the molecules may help the microbes sense dangerous ultraviolet (UV) light in extreme environments.
The latest development has come from a structural biologist called Kirill Kovalev. While browsing online protein databases, Kovalev spotted an unusual feature common to microbial rhodopsins found exclusively in very cold environments, such as glaciers and high mountains.
Kovalev spotted an unusual feature common to microbial rhodopsins found exclusively in very cold environments (from genera like Cryobacterium and Subtercola). These cold-climate rhodopsins were almost identical to each other, even though they evolved thousands of kilometres apart. Kovalev reasoned they must be essential for surviving in the cold, and he subsequently named them ‘cryorhodopsins’.
Colour matters
Colour is the key feature of each rhodopsin. Most are pink-orange – they reflect pink and orange light, and absorb green and blue light, which activates them. Blue rhodopsins have been especially sought-after because they are activated by red light, which penetrates tissues more deeply and non-invasively. The colour of each rhodopsin is determined by its molecular structure, which dictates the wavelengths of light it absorbs and reflects. Any changes in this structure can alter the colour.
Kovalev applied a 4D structural biology approach, combining X-ray crystallography at EMBL Hamburg beamline P14 and cryo-electron microscopy (cryo-EM). This showed that many of the cryorhodopsins were blue. When cells expressing cryorhodopsins were exposed to UV light, it induced electric currents inside them. Interestingly, when Kovalev illuminated the cells right afterwards with green light, the cells became more excitable, whereas if they used UV/red light instead, it reduced the cells’ excitability.
It is reasoned that cryorhodopsins might act like photosensors letting the microbes ‘see’ UV light.
Synthetic blue
Applying advanced structural biology techniques, Kovalev figured out that the secret to the blue colour is the same rare structural feature that he originally spotted in the protein databases.
Applying advanced structural biology techniques, Kovalev figured out that the secret to the blue colour is the same rare structural feature that he originally spotted in the protein databases. “Now that we understand what makes them blue, we can design synthetic blue rhodopsins tailored to different applications,” explains Kovalev.
This extends to the remarkable ability to turn cellular electrical activity on and off. Kovalev believes the molecules could one day power new brain technology, such as light-based hearing aids or next-level neuroscience tools.
The research appears in the journal Science Advances, titled “CryoRhodopsins: A comprehensive characterization of a group of microbial rhodopsins from cold environments.”
