Findings on Color Vision Published in *Science*
The human eye contains about six million cones. They are found primarily in the central region of the retina and, in addition to color vision, are responsible for spatial and sharp vision in daylight. In twilight or darkness, the rod cells located further out take over, though they only enable black-and-white vision. While the mechanism for the rod pigment, rhodopsin, has been known for 25 years, the structure and mechanisms of the color opsins remained unclear until now.
This was primarily because the opsins were not available for laboratory studies for a long time. The research partner at Nanchang University succeeded in producing and isolating these proteins in cell cultures. For the studies, the challenge was to activate them with light and preserve this state. Using cryo-electron microscopy at the Institute of Medical Physics and Biophysics at Charité in Berlin, the researchers were then able to generate high-resolution two-dimensional images in the Ångström range, allowing them to identify individual amino acids. From these, the researchers were able to reconstruct the detailed 3D structure of the opsins.
Of particular interest is how a small molecule called retinal is embedded within the three opsins. Retinal reacts to light by folding, thereby triggering a complex signaling cascade that ultimately transmits the stimulus to the brain. The team was able to show that the three opsins differ in terms of which amino acids surround the retinal. This, in turn, influences how the molecule reacts to light of different wavelengths, enabling the opsins to detect blue, green, or red light. Thus, colored light stimulates the different cones to varying degrees, and through their combination and complex processing, this gives rise to color perception in the brain.
Simulations Explain Light Sensitivity
Computer simulations from the research group led by Prof. Igor Schapiro at TU Dortmund University were crucial for understanding the molecular structures. The Dortmund-based researchers Probal Nag and Leon Busche conducted so-called multiscale simulations—that is, combined quantum mechanical and molecular mechanical calculations—which allow for a particularly precise examination of the interaction between light-sensitive retinal and its surroundings within the respective opsin.
“Cryo-electron microscopy reveals the molecular structure of the proteins. With our simulations, we can refine this data and also understand how retinal reacts electronically in this environment,” says Prof. Igor Schapiro. “It is precisely these electronic properties—which are determined by the respective amino acids in the proteins—that determine which wavelengths of light a pigment absorbs—and thus whether it responds more to blue, green, or red light.”
The simulations conducted in Dortmund showed that the experimentally determined structures surrounding retinal match the properties of the opsins that could be measured spectroscopically. They therefore support the study’s central conclusion that small differences in the amino acid environment surrounding retinal are sufficient to specifically shift the light sensitivity of the three human color opsins.
The study was conducted under the joint leadership of Dr. Patrick Scheerer (Charité) and Prof. Jin Zhang (Nanchang University, China). In addition to the team led by Prof. Igor Schapiro from TU Dortmund University, researchers from the Chinese universities of Shenzhen and Ganzhou and the Australian National University in Canberra were also involved.