Tyton parasites serve a person

The inability to get a large number of membrane proteins is a “narrow place” for their study. Scientists of the Center for Research of Molecular Mechanisms of Style and Age Diseases of the Moscow Physical and Technical Institute for the first time applied an alternative to the artificial developing of Lexsy protein from the cells of the Titon parasite for the production of receptors associated with the G-Belkom. It allowed you to get three times more test protein than the standard systems used for this. The study is told by the press service of the MIPT.

The receptors associated with the G-Belkom (GPCR) form the largest super family of membrane proteins in the human genome (more than 800). These tiny molecular "machines" built into the walls of the cells interact between the inside of the cell and the external environment. It is not surprising that they are crucial in the development of drugs. But in order to more accurately aim the molecule of the medicine on your target, you need to know the atomic structure of the receptor. Today, they are determined only in 20 % of these proteins. The experiments require a large amount of biomaterial. Human proteins cannot be distinguished from people, they are grown in artificial systems. Most often, to create GPCR systems, scientists use moten egg eggs - corn deciduous scoop. They place human DNA, using a virus attacked by insects, which produces protein desired for research. This process is called recombinant expression. The produced protein is released from the cell and cleaned of impurities. Only after this can various methods study its atomic structure or biophysical properties.

A senior researcher at the Laboratory of structural biology of receptors associated with G-Belkom, MFTi Alexander Luginin explains: “Transmembrane proteins are basically quite difficult to develop in artificial systems. Structural studies need large quantities of quality protein. But some proteins are not possible. We were looking for conditions in which you could get such proteins . ”

Scientists of the Center for Research of Molecular Mechanisms of Style and Age Diseases of the MIF decided to try to get such proteins using leishmania - unicellular parasitic creatures. In the experiments, Leishmania Tarentolae Tribona Tytons were used for the expression of GPCR (Lexsy - Leishmania Expression System). Biophysicists for the testing of the Lexsy system has developed with its help an adenosine receptor (A2AAR) - a model and well -studied representative of the family. The resulting protein was compared with the same receptor produced in insect cells. He showed similar purity, stability and structural dynamics. But in Lexsy cells it turned out noticeably more, which greatly pleased scientists.

Deputy Director of the Center for Research of Molecular Mechanisms of Antiquity and Age Diseases MFTi Valentin Borschevsky comments: “In general, our results show that Lexsy is a promising platform for large -scale production of GPCR and other transmembrane proteins for structural studies . ”

The Lexsy Expression System showed a promising result. It is able to produce functional and stable membrane proteins similar to those that are obtained in more traditional systems such as insect cells or mammals. Its ability to express receptors associated with G-Belk, with a high output, can add a convenient and effective tool to the arsenal of experimenters and have a decisive effect on further structural and functional studies. In addition, the Lexsy expression system is a quick and economical alternative to more established expression methods. The team of scientists from MIPT believes that Lexsy will replenish the piggy bank of the spatial structures of GPCR, which will ultimately lead to a simplification of the search for drugs and therapeutic developments.

The work is published in the Journal of Molecular Biology. The study was supported by the Russian Scientific Fund (22-74-00024).