[2020-05-11] When 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 Thermusthermophilus 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, https://doi.org/10.1038/s41589-020-0520-2
Link to the publication
Contact:
Vasili Hauryliuk, associate professor
The Laboratory for Molecular Infection Medicine Sweden (MIMS)
Umeå Centre for Microbial Research (UCMR)
Umeå University
http://www.mims.umu.se/groups/vasili-hauryliuk.html
This email address is being protected from spambots. You need JavaScript enabled to view it.
Top picture: Structure of RelTtNTD in a resting and closed state. a, Structure of RelTtNTD in the resting, nucleotide-free state. The HD domain is colored light blue, the α9–α10 α-helical substructure connecting the HD and the SYN domains is colored light green and the SYN domain is colored orange. b, Structure of RelTtNTD in the active hydrolase state. (figure from the publication in Nature Chemical Biology)