Abstract：
:Bifunctional Rel stringent factors, the most abundant class of RelA/SpoT homologs, are ribosome-associated enzymes that transfer a pyrophosphate from ATP onto the 3' of guanosine tri-/diphosphate (GTP/GDP) to synthesize the bacterial alarmone (p)ppGpp, and also catalyze the 3' pyrophosphate hydrolysis to degrade it. The regulation of the opposing activities of Rel enzymes is a complex allosteric mechanism that remains an active research topic despite decades of research. We show that a guanine-nucleotide-switch mechanism controls catalysis by Thermus thermophilus Rel (RelTt). The binding of GDP/ATP opens the N-terminal catalytic domains (NTD) of RelTt (RelTtNTD) by stretching apart the two catalytic domains. This activates the synthetase domain and allosterically blocks hydrolysis. Conversely, binding of ppGpp to the hydrolase domain closes the NTD, burying the synthetase active site and precluding the binding of synthesis precursors. This allosteric mechanism is an activity switch that safeguards against futile cycles of alarmone synthesis and degradation.
journal_name
Nat Chem Bioljournal_title
Nature chemical biologyauthors
Tamman H,Van Nerom K,Takada H,Vandenberk N,Scholl D,Polikanov Y,Hofkens J,Talavera A,Hauryliuk V,Hendrix J,Garcia-Pino Adoi
10.1038/s41589-020-0520-2subject
Has Abstractpub_date
2020-08-01 00:00:00pages
834-840issue
8eissn
1552-4450issn
1552-4469pii
10.1038/s41589-020-0520-2journal_volume
16pub_type
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