Scientists from MIPT, together with foreign colleagues, were among the first in the world to discover and study the high-resolution structure of a protein from a new family of heliorodopsins. At one time, the discovery of channel rhodopsins led to the advent of optogenetics - a technique for controlling nerve or muscle cells in a living organism using light.
The work was published in the journal PNAS .
Optogenetics that appeared in 2005 year, based on the introduction of special proteins into the membrane of neurons - opsins, which respond to excitation by light. Research in this area has opened up new possibilities in the treatment of Parkinson's disease, depression, anxiety and epilepsy.
Rhodopsins belong to an extensive group of opsins. These proteins contain a special group - retinal, upon absorption of a photon which protein is activated. Until the beginning of the 21st century, only archaeal rhodopsins found in the genomes of halobacteria were studied. However, to date, with the help of genomic and metagenomic studies, more of thousands of rhodopsin genes have been found. Rhodopsins are present in all three domains of life (bacteria, archaea, eukaryotes) and in giant viruses and make the main contribution to the capture of solar energy in the ocean.
Huge variety proteins, their biological importance and numerous biotechnological applications create the need to study their structure. Understanding the structure of a protein helps determine the mechanisms of action and even function. The staff of the Center for Research on the Molecular Mechanisms of Aging and Age-Related Diseases of the Moscow Institute of Physics and Technology has traditionally made a major contribution to the development of this field. Last year, the center’s employees deciphered the structures of the KR2 protein and rhodopsin from a giant virus.
Despite the differences in the properties and structures of rhodopsins, their orientation in the membrane is usually the same. Proteins have two ends, called N- and C-, by the presence of an amino and carboxyl group, respectively. All known rhodopsins are oriented in the membrane so that the N-terminal fragment is outside the cell. However, in the recently discovered family of heliorodopsins, everything is turned upside down: the N-terminus is located inside the cell. The laboratory staff for the first time deciphered the structure of a representative of this family, protein 12 C , shows the key differences from the known rhodopsins and makes an assumption about the function of heliorodopsins.
Kirill Kovalev , one of the first authors of the work, graduate student of MIPT, says:
“Heliorodopsins are unusual proteins. The high-resolution structures we obtained demonstrated both their unique global architecture and the details of the internal structure and interactions between key amino acid residues. ”
In their work, scientists were able to analyze the structure of the protein 12 C 12 in two states and compare it with the structures of other microbial rhodopsins. So, it was shown that inside the protein, in its cytoplasmic part, there is a large cavity filled with a large number of water molecules. In one of the obtained protein states, an acetate molecule was detected in the cavity. Thus, the cavity can play the role of an “active center” of the protein in which the binding of a substrate such as nitrate or carbonate occurs.
Despite this assumption of the authors, the function and biological role of heliorodopsins remains unknown.
Valentin Gordeliy , scientific Coordinator of the Center for Research on Molecular Mechanisms of Aging and Age-Related Diseases, MIPT, explains:
“So unusual protein structure and its properties allow us to suggest the enzymatic function of heliorodopsins. In addition, our work showed that protein groups with different functions can be distinguished among this family. ”
Thus, the scientists deciphered the structure of heliorodopsin 12 C 12 and showed a fundamental difference from other microbial rhodopsins. The results of this work open up new possibilities for the further study of heliorodopsins.
The work was supported by the Russian Science Foundation and the Russian Foundation for Basic Research.