Recently identified protein group plays major role in nature
Go"ttingen University researchers find protein switch they discovered regulates enzymes in pathogens

Date:
February 16, 2022
Source:
University of Go"ttingen
Summary:
Proteins are the 'workhorses' in every living cell and constitute
the chemical basis of life. These little machines are required to
turn food into energy, to manage motion and brain activities and to
fight off bacteria and viruses. The function of proteins is tightly
controlled in response to changing conditions, when for instance
an organism encounters stress and needs to adapt. Researchers
recently discovered a completely novel group of proteins that
functions as a switch to regulate biological activity. Now they
have analyzed all known protein structures and it turns out that
this group exists in all domains of life, in viruses and bacteria
as well as in fungi, plants and animals, including humans. These
findings have far-ranging implications for the treatment of many
diseases. The results were published in Nature Chemical Biology.



FULL STORY ========================================================================== Proteins are the "workhorses" in every living cell and constitute the
chemical basis of life. These little machines are required to turn food
into energy, to manage motion and brain activities and to fight off
bacteria and viruses. The function of proteins is tightly controlled in response to changing conditions, when for instance an organism encounters stress and needs to adapt. Researchers at the University of Go"ttingen
recently discovered a completely novel group of proteins that functions
as a switch to regulate biological activity. Now they have analyzed all
known protein structures and it turns out that this group exists in all
domains of life, in viruses and bacteria as well as in fungi, plants and animals, including humans. These findings have far-ranging implications
for the treatment of many diseases. The results were published in Nature Chemical Biology.


==========================================================================
The Go"ttingen University team initially discovered the new protein switch
- - known as a "NOS switch" because Nitrogen, Oxygen and Sulphur atoms are connected -- in a protein from the human pathogen Neisseria gonorrhoeae.

However, the question remained whether this switch was widespread
in nature.

The researchers have now analyzed the entire database of known protein structures held in a publicly accessible repository for hitherto
undetected NOS switches. The computational analysis by first author Dr
Fabian Rabe von Pappenheim, University of Go"ttingen, produced hundreds of hits, which were then all individually analysed in detail. "Investigating
these structures was an exciting endeavour. It was like travelling
into the unknown for us," recalls Professor Kai Tittmann, University of Go"ttingen, who led the study.

The novel NOS switch was found to exist across all domains of life,
and often at sites of proteins that are essential for biological
function. Remarkably, numerous proteins from some of the most dangerous
human pathogens have this switch, including a key enzyme from the
SARS-CoV-2 coronavirus. In fact, this switch is a target for the
recently approved antiviral drug for patients with mild to modrerate
Covid-19 who might be at high risk of developing serious disease. In
addition, the researchers discovered several new chemical forms of the
NOS switch, which turns out to be a universally used regulation platform
in biology. The identified proteins play central roles in almost every
aspect of cellular activities, be it the expression of genes, signalling
in and between cells, or metabolism.

"We believe that the discovery of these new protein switches will
be a springboard for the development of a novel class of drugs
that directly targets these switches," says Tittmann. "Many
human proteins with known roles in severe diseases as well as
proteins from bacteria and viruses are now known to be controlled
by such switches. The newly identified switch is likely to play
a central role in regulating their biological function as well." ========================================================================== Story Source: Materials provided by University_of_Go"ttingen. Note:
Content may be edited for style and length.


========================================================================== Related Multimedia:
* Illustration_of_NOS_and_SONOS_protein_groups ========================================================================== Journal Reference:
1. Fabian Rabe von Pappenheim, Marie Wensien, Jin Ye, Jon Uranga, Iker
Irisarri, Jan de Vries, Lisa-Marie Funk, Ricardo A. Mata, Kai
Tittmann.

Widespread occurrence of covalent lysine-cysteine redox
switches in proteins. Nature Chemical Biology, 2022; DOI:
10.1038/s41589-021-00966-5 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/02/220216130317.htm

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