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Researchers observe vital cellular machinery behind the body’s incorporation of selenium

Onderzoekers observeren vitale cellulaire machinerie achter de opname van seleniumScience (2022). DOI: 10.1126/science.abg3875″ width=”782″ height=”530″/>

CryoEM analysis of the 80S Selenosome dataset. (A) Representative cryoelectron micrograph of the fully assembled 80S-selenosome sample. Scale bar represents 50 nm in the image. (B) Class means after reference-free 2D classification generated with cryoSPARC. (C) Resolution estimation by gold standard Fourier shell correlation. (D) Angle distribution plot after NU refinement with cryoSPARC shows a moderate orientation bias that did not appear to be limiting for the reconstruction. (E) Local resolution as determined by cryoSPARC. The cryoEM density surface is stained according to the resolution estimates ranging from 2.3 (blue) to 10.3 (red) imaged from the view of the GAC (left) and rotated 180° (right). Low-resolution regions are mainly in the periphery. Credit: Science (2022). DOI: 10.1126/science.abg3875

A Rutgers scientist is part of an international team that determined the process for absorbing selenium – an essential trace mineral found in soil, water and some foods that increase antioxidant effects in the body – includes 25 specialized proteins, a discovery that could help develop new therapies to treat a wide range of diseases, from cancer to diabetes.

The research, detailed in Science, contains the most in-depth description yet of the process by which selenium gets where it needs to be in cells, which is critical to many aspects of cell and organism biology. First, selenium is encapsulated in selenocysteine ​​(Sec), an essential amino acid. Then Sec is incorporated into 25 so-called selenoproteins, all of which are key to numerous cellular and metabolic processes.

According to researchers, including Paul Copeland, a professor in the Department of Biochemistry and Molecular Biology at Rutgers Robert Wood Johnson Medical School, understanding the functioning of these vital mechanisms in such a detailed manner is critical for the development of new medical therapies.

“This work revealed structures never seen before, some of which are unique in all of biology,” said Copeland, an author of the study.

Copeland and team were able to visualize the cell mechanisms using a specialized cryoelectron 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 — leveraging today’s massive computing power to string together thousands of images to produce three-dimensional cross-sections and even stop-motion animation that conveys a sense of motion in the biomolecules. . As a result, scientists can see representations of the intricate structure of proteins and other biomolecules and even how these structures move and change as they function as cellular ‘machines’.

Selenium uptake occurs deep within the intricate machinery of an individual cell. Scientists already knew which proteins and molecules of RNA – a nucleic acid present in all cells involved in the production of proteins – made the process possible. However, they were unable to discern the crucial step of how these factors worked together to complete the cycle, which dictated the function of the cell’s ribosome — a large macromolecular machine that binds RNA to make more proteins. What they found was that the processes that take place are not the way they are thought to take place elsewhere in the human body.

“This amino acid attaches to a unique RNA molecule, and that must be transported to the ribosome via a unique protein factor,” said Copeland, whose lab has spent the past 20 years working to understand how these biomolecules function at the biochemical level. “And all of this evolved specifically in humans to incorporate selenium into this handful of proteins.”

Once Sec is anchored in the selenoproteins, the proteins perform a wide variety of vital functions necessary for growth and development. They produce nucleotides, the building blocks of DNA. They break down fat or store it for energy. They make cell membranes. They produce the thyroid hormone, which regulates the metabolism of the human body. And they respond to what’s known as oxidative stress by detoxifying chemically reactive byproducts in cells.

Diseases and conditions such as cancer, heart disease, male infertility, diabetes, and hypothyroidism can develop when selenoprotein production is disrupted.

“Understanding the mechanism by which Sec is taken up is a fundamental part of developing new therapies for a wide range of disease states,” Copeland said.


Researchers discover how selenium is built into proteins


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

Provided by Rutgers University


Quote: Researchers observe vital cellular machinery behind the body’s uptake of selenium (2022, June 17) Retrieved June 17, 2022 from https://phys.org/news/2022-06-vital-cellular-machinery-body-incorporation. html

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