Humans need eight essential trace elements for good health, and one of them is selenium -- a powerful antioxidant that is important for thyroid and brain function as well as metabolism. Researchers have now discovered exactly how selenium is incorporated into selenoproteins.
Background:
Trace elements can't be used by the body until they are integrated
into a protein molecule. Selenium is unique because it is folded into
its protein while the protein molecule is still being made. All other
trace elements are added to their respective protein molecules after the
cell has finished synthesizing the protein.
The new study:
Researchers at the University of Illinois at Chicago have discovered
exactly how selenium is incorporated into selenoproteins. The finding is
published in the journal Nature Communications.
Proteins are made by linking amino acids together, one
at a time, in a chain. Cellular structures called ribosomes serve as
docking stations, where all the components involved in protein
production come together -- messenger RNA, which serves as the protein's
blueprint; the amino acid building blocks, each attached to its own
specific transfer RNA; and various helper molecules. Elongation factors
are an important type of helper protein that guide the amino acids to
the ribosome during protein synthesis. In humans, elongation factor
eEF1A helps string together amino acids at the ribosome -- that is, all
amino acids except selenocysteine, the amino acid that holds selenium.
In humans, selenocysteine is incorporated into proteins with help of a
unique elongation factor called eEFSec that works very differently from
eEF1A. "We've known that selenium is special when it comes to protein
synthesis, because there is a whole other set of rules and tools in
use," says Miljan Simonovic, associate professor of biochemistry and
molecular genetics in the UIC College of Medicine and corresponding
author on the paper. "Not only does it have its own elongation factor,
but selenocysteine is also very unusual because it is represented in the
genetic code by the same three-letter key, or codon, that signals for
protein synthesis to stop."
Normally, as the ribosome reads the messenger RNA -- or mRNA -- and
reaches this stop codon, it detaches from the mRNA because its work is
done, although the full-length protein may still be modified through
other processes.
But sometimes the ribosome runs the stop sign and adds selenocysteine
instead -- and continues to elongate the protein until it reaches
another stop sign. "When the stop codon means 'bring in a
selenocysteine,' additional protein factors together with structural
features in the mRNA around that stop codon, such as loops, indicate to
the ribosome not to stop selenoprotein production," said Malgorzata
Dobosz-Bartoszek, postdoctoral research associate in biological
sciences, who is lead author on the paper. "The selenocysteine
elongation factor, eEFSec, plays a key role in helping to recognize the
stop codon as actually coding for selenocysteine."
Simonovic said the eEFSec elongation factor also stands apart in how
it changes shape when it delivers selenocysteine to the ribosome. The
researchers showed that eEFSec bends about 20 degrees when delivering
selenocysteine, while eEF1A bends "much more dramatically -- more like
90 degrees" when it drops off the other amino acids.
Simonovic thinks that the reason selenocysteine is handled so
differently during protein synthesis traces back to the Great
Oxygenation Event. This was the period about 2.3 billion years ago when
free oxygen in Earth's atmosphere suddenly spiked, due to the
evolutionary emergence of plants and photosynthesis as a way to derive
energy from the sun. Organisms needed to evolve ways to prevent cellular
damage caused by oxidation, and selenium, a powerful antioxidant, would
have been available. But already-existing processes for incorporating
trace elements into proteins may not have worked for selenium, which is
extremely reactive.
"We know that eEFSec has a unique domain that helps it safely interact with selenocysteine," Simonovic said.
Story Source:
Materials provided by University of Illinois at Chicago. Note: Content may be edited for style and length.
The original study
Malgorzata Dobosz-Bartoszek, Mark H. Pinkerton, Zbyszek Otwinowski, Srinivas Chakravarthy, Dieter Söll, Paul R. Copeland, Miljan Simonovic. Crystal structures of the human elongation factor eEFSec suggest a non-canonical mechanism for selenocysteine incorporation. Nature Communications, 2016; 7: 12941. doi: 10.1038/ncomms12941
Related studies (newest first)
M.P. Rayman, Selenoproteins and human health: insights from epidemiological data. Biochim. Biophys. Acta, 1790 (2009) 1533–1540. doi: 10.1016/j.bbagen.2009.03.014
Gregory V. Kryukov, Sergi Castellano, Sergey V. Novoselov, Alexey V. Lobanov, Omid Zehtab, Roderic Guigó, Vadim N. Gladyshev, Characterization of Mammalian Selenoproteomes, Science, 300 (2003) 1439-1443. doi: 10.1126/science.1083516
Related EVISA Resources
Link database: All about proteins containing selenium
Link database: Selenium and human health
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last time modified: September 24, 2024
