US researchers have discovered the molecular mechanisms by which the human body metabolizes selenium, a trace element that plays an essential role in helping enzymes defend against disease; and suggest their findings will have wide implications for human health, including areas like the immune response, neurodegeneration, cardiovascular disease, and cancer.
The study was the work of researchers at Yale University in New Haven, Connecticut, and the University of Illinois at Chicago, and is published in the 17 July issue of Science.
The trace element selenium is crucial for life: yet too little or too much is fatal. It is found in 25 human selenoproteins, most of them essential for life, said co-senior author Dr Dieter Söll, Sterling Professor of Molecular Biophysics and Biochemistry at Yale.
“It must require an intricately regulated uptake system,” he added.
Other studies have suggested that the trace element protects against a range of conditions and diseases, including adverse mood states, viral infections, cardiovascular disease, and cancer.
The most active metabolite of selenium found in the human body is the protein selenocysteine, which is unique in that it is the only one that is synthesized directly on a transfer RNA (tRNA) molecule. The authors described this feature thus:
“Selenocysteine is the only genetically encoded amino acid in humans whose biosynthesis occurs on its cognate transfer RNA (tRNA).”
Proteins are essential compounds that regulate all aspects of growth, maintenance and development in the body, and while DNA holds the blueprint for making them, the genetic machinery that builds protein molecules is made of RNA, and transfer RNA or tRNA is a type of RNA that shuttles amino acids into cells where they are made into proteins.
Proteins made with selenocysteine recycle protective antioxidants such as vitamin C and coenzyme Q10.
For this study the researchers captured images of selenocysteine being made on a super-sized tRNA molecule, which seems to play a very particular role in the body and also has something called an elongation factor for transporting amino acids.
They discovered that while other tRNAs also have elongation factors, the one on this particular supersized tRNA only transports selenocysteine.
Lead author Sotiria Palioura, who is working towards an MD/PhD at Yale, said:
“This structure reveals most aspects of the mechanism for the formation of selenocysteine and provides an answer to 20 years of biochemical work in the field.”
Palioura said the findings may help us better understand the biology of autoimmune liver disease because the tRNA they studied is the same one that is targeted by antibodies in patients with Type 1 autoimmune hepatitis.
“The region that the antibody is supposed to recognize is at the business end of this molecule, where we see the reaction happening,” explained Palioura.
Michael Bender of the National Institutes of Health’s National Institute of General Medical Sciences said that other studies have shown that selenocysteine is a critical component of enzymes involved in a number of normal and disease processes, and now with this study uncovering the protein’s unique biosynthetic pathway, the gathered knowledge:
“Could ultimately have an impact on many aspects of human health, including the immune response, neurodegeneration, cardiovascular disease, and cancer.”
The study was supported by grants from the National Institute for General Medical Sciences, the Department of Energy, and the Howard Hughes Medical Institute at Yale University.
“The Human SepSecS-tRNASec Complex Reveals the Mechanism of Selenocysteine Formation.”
Sotiria Palioura, R. Lynn Sherrer, Thomas A. Steitz, Dieter Söll, and Miljan Simonovic.
DOI: 10.1126/science.1173755
Source: Yale University.
Written by: Catharine Paddock, PhD