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

Science (2022). DOI: 10.1126/science.abg3875″ width=”782″ height=”530″/>

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 means after 2D classification without reference generated with cryoSPARC. (C) Resolution estimation by Fourier-shell-gold standard correlation. (D) The angular distribution plot after NU refinement with cryoSPARC shows moderate orientation bias that was found not to be limiting for reconstruction. (E) Local resolution as determined with cryoSPARC. The cryoEM density surface is colored according to resolution estimates, ranging from 2.3 Å (blue) to 10.3 Å (red) shown from the view on the GAC (left) and rotated 180° (at right). Low-resolution regions mostly reside in the periphery. Credit: Science (2022). DOI: 10.1126/science.abg3875

A Rutgers scientist is part of an international team that has determined the process of incorporating selenium – an essential trace mineral found in soil, water and some foods that increases antioxidant effects in the body – includes 25 proteins medicines, a discovery that could help develop new therapies to treat a host of diseases ranging from cancer to diabetes.

The research, detailed in Science, includes the most detailed description to date of the process by which selenium gets to where it needs to be in cells, which is crucial for many aspects of cell and organismal biology. First, selenium is encapsulated in selenocysteine ​​(Sec), a essential amino acid. Next, Sec is incorporated into 25 so-called selenoproteins, all essential to a host of cellular proteins and metabolic processes.

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

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

Copeland and the team were able to visualize cellular mechanisms using a cryo-electronic microscope, which uses beams of electrons rather than light to form three-dimensional images of complex biological formations at near atomic resolution. The process uses frozen samples of molecular complexes, then applies sophisticated image processing, using today’s vast computing power to string together thousands of images to produce three-dimensional cross-sections and even animation. in stop-motion conveying a sensation of movement in the 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.”

The incorporation of selenium takes place deep within the complex machinery of an individual cell. Scientists already knew which proteins and RNA molecules – a nucleic acid present in all cells involved in protein production – enable the process. However, they were unable to discern the critical step of how these factors worked 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 discovered is that the processes taking place are unlike any other taking place elsewhere in the human body.

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

Once Sec is installed in selenoproteins, the 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 to produce energy. They create cell membranes. They produce the thyroid hormonewho controls the human bodythe metabolism. And they respond to what’s called oxidative stress by detoxifying chemically reactive byproducts in cells.

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

“Understanding the mechanism by which Sec is incorporated is fundamental to the development of novel therapies for a multitude of disease states,” Copeland said.

Researchers discover how selenium is incorporated into proteins

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

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Rutgers University

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