Scientists Map the Eye Protein Structure That Gives the World Color

All the vivid colors of our world would be meaningless to humans without cone opsins. These are receptor proteins bundled up within the retina. In response to light, these opsins spring to life, rendering the vivid red of a rose or the deep blue of the ocean. But when opsins malfunction, there can be serious consequences. Cone opsin issues underlie the vision-eroding condition age-related macular degeneration (AMD), for example.

To understand how cone opsins paint the world, scientists have longed to study them in their dark, inactivated state. But these proteins are so sensitive to light that this endeavor has proved too difficult, until now. In a new paper published today in Science, an international research team has reported the first three-dimensional structure of inactivated cone opsins, which will make it easier to design drugs targeting the protein, potentially accelerating therapies for AMD and related conditions.¹

Bringing Cones into the Light

Cone opsin proteins are found in cone cells, located in the retina’s center, the fovea centralis. The proteins, once stimulated by light, rapidly send electrical signals to the brain. The speed of these signals lets the eye track moving objects. The three cone opsins, L, M, and S, enable the detection of red, green, and blue light, respectively, which combine to reveal the full color spectrum. Cone opsins are most useful during bright daylight hours. In low-light conditions, the eyes rely on rod opsins, found in rod cells.

Unfortunately, biomedical research labs are some of the brightest conditions around. To avoid activating cone cells, the scientists conducted their new study under dim red light that sat outside the wavelengths the cones could detect. By combining digital, biophysical, and cellular assays, the team revealed the structures of the blue and green cone opsins. Evolutionary principles suggest that the red cone opsin, although they did not study it directly, is likely to match its closely related green counterpart.

How Cones Became Honed to Their Task

The findings revealed that the cone opsin proteins have become specialized for their tasks. “Our new structural and functional data indicate that cone opsins are optimized for rapid signal transmission,” said Sarah Schmidt, a biomolecular scientist at the Paul Scherrer Institute (PSI) and coauthor of the new study, in a statement. This includes a network of “microswitches” that link to a partner G protein. The strength of the connection within the cone opsins in the resting state explains how the protein network can then rapidly fire up upon activation.

The researchers’ analysis revealed other ways in which the cone opsins are specialized for their task. A molecular “pocket” within the opsin binds a light-sensitive molecule called retinal, which absorbs light energy to trigger electrical impulses in the retina. Schmidt and her team found that the retinal-binding pocket in green cone opsin is relatively open, allowing molecules to rapidly transit through it as light hits the eye. The blue cone opsin’s binding site is more cramped, which means a stronger energy impulse is required to induce a response in the retinal molecule. This is suited to blue light, which is higher in energy than red or green light.

The researchers hope their findings could help researchers put new therapies for AMD into focus, by accelerating the development of drugs that stabilize and support cone opsins. “A detailed structural understanding of these mechanisms helps us identify where things go wrong in such diseases and where targeted therapies might be possible,” said Polina Isaikina, a biomolecular scientist at the PSI and coauthor of the new study, in the statement.