Researchers are monitoring vital cellular machines behind the incorporation of selenium into the body

Изследователите наблюдават жизненоважни клетъчни машини зад включването на селен

CryoEM analysis of the 80S-Selenosome dataset. (A) Representative cryo-electron micrograph of the fully assembled 80S-selenosome sample. The scale bar represents 50 nm in the image. (B) Class averages after 2D classification without reference data generated by cryoSPARC. (C) Estimation of the resolution by correlation of the Fourier casing according to the gold standard. (D) The graph of the angular distribution after NU improvement with cryoSPARC shows a moderate deviation in orientation, which turned out not to be limiting for the reconstruction. (E) Local resolution as determined by cryoSPARC. The cryoEM density surface was stained according to resolution estimates ranging from 2.3 Å (blue) to 10.3 Å (red), depicted from a GAC ​​view (left) and rotated 180 ° (right). The low-resolution regions are mainly located on the periphery. credit: science (2022). DOI: 10.1126 / science.abg3875

A Rutgers scientist is part of an international team that has identified the process of incorporating selenium – a key trace element found in soil, water and certain foods that enhances antioxidant effects in the body – including 25 specialized proteins, a discovery that could help develop of new therapies for the treatment of many diseases from cancer to diabetes.

The study, described in detail in science, includes the most in-depth description of the process by which selenium reaches where it should be in cells, which is crucial for many aspects of cell and body biology. First, selenium is encapsulated in selenocysteine ​​(Sec), an essential amino acid. Sec is then involved in 25 so-called selenoproteins, all of which are key to multiple cellular and metabolic processes.

Understanding the workings of these vital mechanisms in such detail is crucial to the development of new medical therapies, according to researchers including Paul Copeland, a professor in the Department of Biochemistry and Molecular Biology at Rutgers Medical School Robert Wood Johnson.

“This work has revealed structures that have never been seen before, some of which are unique in all of biology,” said Copeland, the study’s author.

Copeland and the team were able to visualize cellular mechanisms using specialized cryo-electronic microscope, which uses electron beams instead of light to form three-dimensional images of complex biological formations with near-atomic resolution. The process uses frozen samples of molecular complexes and then applies advanced image processing – using enormous computing power today to put together thousands of images to produce three-dimensional cross-sections and even motion-stopped animation that conveys a sense of motion in biomolecules. As a result, scientists can see representations of the complex structure of proteins and other biomolecules, and even how these structures move and change as they function as cellular “machines.”

Selenium incorporation takes place deep into the complex machine of the individual cell. Scientists already knew which proteins and RNA molecules – nucleic acid present in all cells involved in protein production – activated the process. However, they failed to understand the critical step of how these factors work in tandem to complete the cycle, dictating the function of the cell’s ribosome, a large macromolecular machine that binds RNA to make more protein. What they found was that the processes that take place are not like all those that are supposed to take place elsewhere in the human body.

This amino acid attaches to a unique RNA molecule and it must be transferred to the ribosome through a unique protein factor, “said Copeland, whose lab has spent the past 20 years understanding how these biomolecules function at the biochemical level. And all this is evolving in humans specifically to allow selenium to be included in this handful of proteins. “

Once Sec is established in selenoproteins, proteins perform a wide range of vital functions necessary for growth and development. They produce nucleotides, the building blocks of DNA. They break down or store fat for energy. They create cell membranes. They produce thyroid hormoneswho controls Human bodymetabolism of. And they respond to what is known as oxidative stress by detoxifying chemically reactive by-products in cells.

Diseases and disorders such as cancer, heart diseasemale infertility, diabetes and hypothyroidism can occur when selenoprotein production is impaired.

“Understanding the mechanism by which Sec is involved is a fundamental part of developing new therapies for many disease states,” Copeland said.

Researchers have discovered how selenium is incorporated into proteins

More info:
Tarek Hilal et al, Structure of the mammalian ribosome as it decodes the selenocysteine ​​UGA codon, science (2022). DOI: 10.1126 / science.abg3875

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Quote: Researchers Observe Vital Cellular Machines Behind the Incorporation of Selenium in the Body (2022, June 17) Extracted on June 17, 2022 from .html

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