For the first time ever, researchers were able to characterize the three-dimensional interactions between red light receptors and effectors within enzymes. The results of the research could have implications in the field of optogenetics.
[Translation by Dr. Nachmani Moshe]
The purpose of optogenetics is to control genetically modified cells using light. A team of scientists from the University of Graz is responsible for an important advance in the future development of innovative optogenetic tools controlled by red light for targeted stimulation of cells. For the first time ever, researchers were able to observe the molecular principles underlying detector-effector coupling in the complete structure of a protein that responds to red light and describe in detail the mechanisms of signal transmission across a long pathway at the molecular level. The results have long been published in the scientific journal Science Advances.
In order to exist, cells and living things must adapt to new conditions in the environment. This is the responsibility of the building blocks of proteins that react with each other in different ways, creating cellular networks that allow adaptation to changing environmental conditions. The detectors, or "receptors" responsible for receiving external stimulus signals, such as light, are connected to effectors, with the aim of activating or deactivating defined molecular signaling molecules, according to the immediate need of the cell. The researchers now reveal the molecular details of a red light photoreceptor involved in the production of an important messenger molecule, and describe the complete structure of the receptor along with the enzyme effector. The structure and composition of the link factor connecting the detector and the effector are very important in light regulation. "Through a combination of structural analysis with the help of X-ray crystallography and the replacement of hydrogen atoms with deuterium atoms, with the help of which the structural dynamics and changes in the space of the various atoms can be measured, we were able to better understand the functional characteristics of this helical connecting factor. We were able to show that the illumination of the detector with red light led to a rotation-like change in the helical binding part, a rotation which in turn affects the enzymatic activity of the neighboring effector", explains one of the researchers.
The research contributes to a better understanding of the modularity of protein complexes that occur in nature and could enable the development of new optogenetic tools. In nature there are various combinations of detector components, for example red light detectors, blue light detectors and acidity level detectors - sometimes together with identical effectors and sometimes completely different. From this finding, the researchers concluded that there is a molecular analogy in signal transmission, and therefore it is worthwhile to develop both rational and completely random combinations of detectors and effectors that do not exist in nature. "Today we are limited by using the systems that exist in nature only within the direct regulation of enzyme functions. Our long-term goal is to create new systems for light regulation that can overcome the limitations that exist in nature and that will be of great importance for various applications in the field of optogenetics."
One response
Amazing. It is indeed hard (but monotonous) work of forming proteins and believing in the correctness of the researchers' initial "guess" for many years, without clear results in the first years, but still with the will and strength to continue. It's literally a bet on the lives and reputations of those involved. inhale