Breaking bad nucleotides: understanding the regulatory mechanisms of bacterial small alarmone hydrolases.

Ditlev E Brodersen, Adriana Chrenková, Francesco Bisiak

Journal: Trends in microbiology 2024;32(8):769-780

PMID: 38262803

Full Text on Elsevier Science View on PubMed

Abstract

Guanosine tetra- and pentaphosphate nucleotides, (p)ppGpp, function as central secondary messengers and alarmones in bacterial cell biology, signalling a range of stress conditions, including nutrient starvation and exposure to cell-wall-targeting antibiotics, and are critical for survival. While activation of the stringent response and alarmone synthesis on starved ribosomes by members of the RSH (Rel) class of proteins is well understood, much less is known about how single-domain small alarmone synthetases (SASs) and their corresponding alarmone hydrolases, the small alarmone hydrolases (SAHs), are regulated and contribute to (p)ppGpp homeostasis. The substrate spectrum of these enzymes has recently been expanded to include hyperphosphorylated adenosine nucleotides, suggesting that they take part in a highly complex and interconnected signalling network. In this review, we provide an overview of our understanding of the SAHs and discuss their structure, function, regulation, and phylogeny.

Address: Department of Molecular Biology and Genetics, Aarhus University, Universitetsbyen 81, DK-8000 Aarhus C, Denmark.; Department of Molecular Biology and Genetics, Aarhus University, Universitetsbyen 81, DK-8000 Aarhus C, Denmark. Electronic address: [email protected].

DOI: 10.1016/j.tim.2023.12.011

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MeSH Terms: Bacteria, Signal Transduction, Bacterial Proteins, Gene Expression Regulation, Bacterial, Hydrolases, Guanosine Pentaphosphate, Guanosine Tetraphosphate, Phylogeny