Zusammenfassung: | |
The stringent response enables metabolic adaptation of bacteria under stress conditions and is governed by RelA/SpoT Homolog (RSH)-type enzymes. Long RSH-type enzymes encompass an N-terminal domain (NTD) harboring the second messenger nucleotide (p)ppGpp hydrolase and synthetase activity and a stress-perceiving and regulatory C-terminal domain (CTD). CTD-mediated binding of Rel to stalled ribosomes boosts (p)ppGpp synthesis. However, how the opposing activities of the NTD are controlled in the absence of stress was poorly understood. Here, we demonstrate on the RSH-type protein Rel that the critical regulative elements reside within the TGS (ThrRS, GTPase, and SpoT) subdomain of the CTD, which associates to and represses the synthetase to concomitantly allow for activation of the hydrolase. Furthermore, we show that Rel forms homodimers, which appear to control the interaction with deacylated-tRNA, but not the enzymatic activity of Rel. Collectively, our study provides a detailed molecular view into the mechanism of stringent response repression in the absence of stress.
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Lizenzbestimmungen: | CC BY-NC-ND 4.0 Unported - https://creativecommons.org/licenses/by-nc-nd/4.0/ |
Publikationstyp: | Article |
Publikationsstatus: | publishedVersion |
Erstveröffentlichung: | 2020 |
Schlagwörter (englisch): | (p)ppGpp synthetase, glutamic acid, guanosine triphosphatase, homodimer, hydrolase, synthetase, transcription factor Rel, transfer RNA, unclassified drug, amino terminal sequence, Bacillus subtilis, binding site, carboxy terminal sequence, chemical reaction, complex formation, controlled study, crystal structure, deacylation, enzyme activation, enzyme activity, enzyme structure, enzyme synthesis, Escherichia coli, high performance liquid chromatography, homodimerization, in vitro study, in vivo study, molecular weight, mutation, nonhuman, priority journal, protein binding, protein conformation, protein interaction, Streptococcus dysgalactiae, stress, stringent response, Western blotting, (p)ppGpp, alarmone, cryo-EM, enzymatic regulation, homodimerization, RSH-type enzyme, stringent response, X-ray crystallography |
Fachliche Zuordnung (DDC): | 570 | Biowissenschaften, Biologie, 610 | Medizin, Gesundheit |
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