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New publication with Vasili Hauryliuk on "Make it or break it: how bacteria balance production and degradation of the ´magic spot´ signaling alarmone"

Vasili Hauryliuk 1150 MPN squareWhen stressed or starved, bacteria regulate their metabolism by producing signalling molecules called alarmones or ‘magic spots’. In the majority of bacteria, the magic spot compounds are both made and destroyed by a large, complex enzyme called Rel. The question of how Rel switches from making the alarmone to degrading it was finally resolved by an international team from Sweden – Vasili Hauryliuk (MIMS & UCMR) – and Belgium: Jelle Hendrix (Hasselt University) and Abel Garcia-Pino (Université Libre de Bruxelles). The results of this study were published in the high impact journal Nature Chemical Biology ("A nucleotide-switch mechanism mediates opposing catalytic activities of Rel enzymes", 11 May 2020).

The team have studied a Rel enzyme from a thermophilic bacterium Thermus thermophilus using a combination of structural (X-ray), biochemical (enzymology) and biophysical (single molecule FRET assays and Isothermal Titration Calorimetry). Since the T. thermophilus has an optimal growth temperature of about 65 °C, by solving the structures at room temperature the researchers could slow down the enzyme enough to ‘catch’ it in the act of synthesising or degrading the alarmone. It turned out that binding of the substrates to the active site region (domain) that is responsible for synthesis of the ‘magic spot’ allosterically inhibits the domain responsible for its degradation – and vice versa, binding of the substrates to the degradation domain inhibits the synthesis domain. This simple but elegant mechanism ensures that bacteria avoid wasteful production and degradation of the magic spot signalling molecule. Biochemical characterisation of T. thermophilus was performed in Umeå by Dr. Hiraku Takada who is supported by a personal postdoctoral fellowship from the Umeå Centre for Microbial Research (UCMR).

This study also involved researchers from the following organisations:
Cellular and Molecular Microbiology, Faculté des Sciences, Université Libre de Bruxelles, Belgium
Molecular Imaging and Photonics, Chemistry Department, KU Leuven, Belgium
Dynamic Bioimaging Laboratory, Advanced Optical Microscopy Centre and Biomedical Research Institute, Hasselt University, Belgium
WELBIO, Brussels, Belgium
Department of Biological Sciences, College of Liberal Arts and Sciences, University of Illinois at Chicago, USA

Original publication:
Hedvig Tamman, Katleen Van Nerom, Hiraku Takada, Niels Vandenberk, Daniel Scholl, Yury Polikanov, Johan Hofkens, Ariel Talavera, Vasili Hauryliuk, Jelle Hendrix and Abel Garcia-Pino. A nucleotide-switch mechanism mediates opposing catalytic activities of Rel enzymes. Nature Chemical Biology, 11 May 2020. To read the full article, please visit Nature Chemical Biology website here

About the Hauryliuk lab
Vasili Hauryliuk is a specialist in protein microbial synthesis, antibiotic resistance and stress responses using a combination of biochemical, microbiological, functional genomics and structural biology methods. The Hauryliuk lab works closely with the group of Gemma C. Atkinson (UCMR, Umeå) who perform advanced evolutionary analyses that guide the experimental work performed in the Hauryliuk lab.

Contact person:
Vasili Hauryliuk, associate professor
The Laboratory for Molecular Infection Medicine Sweden (MIMS)
Umeå Centre for Microbial Research (UCMR), Department of Molecular Biology, Umeå University
This email address is being protected from spambots. You need JavaScript enabled to view it.

Picture: Vasili Hauryliuk by MIMS

 

Battling antibiotic resistance

movie by Knut and Alice Wallenberg Foundation, with participation of scientists from MIMS and UCMR:
Or watch the original movie on:
https://kaw.wallenberg.org/

Research about infectious diseases:

Oliver Billker in movie of Knut and Alice Wallenberg Foundation:
Or watch the original movie on:
https://kaw.wallenberg.org/

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