Structural basis for c-di-AMP–dependent regulation of the bacterial stringent response by receptor protein DarB

Heidemann, Jana L.; Neumann, Piotr; Krüger, Larissa; Wicke, Dennis; Vinhoven, Liza; Linden, Andreas; Dickmanns, Achim; Stülke, Jörg; Urlaub, Henning; Ficner, Ralf

doi:10.1016/j.jbc.2022.102144

Cited by 12 publications

(11 citation statements)

References 53 publications

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“…In our structure, c-di-AMP adopts a U-shaped pose similar to that previously observed in other complexes [38][39][40]. One of the adenine moieties of c-di-AMP is deeply buried into a hydrophobic cavity that serves as the primary site for the protein-nucleotide interaction (Fig.…”

Section: The C-di-amp Binding Sitesupporting

confidence: 76%

The c‐di‐AMP‐binding protein CbpB modulates the level of ppGpp alarmone in Streptococcus agalactiae

et al. 2023

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Cyclic di‐AMP is an essential signalling molecule in Gram‐positive bacteria. This second messenger regulates the osmotic pressure of the cell by interacting directly with the regulatory domains, either RCK_C or CBS domains, of several potassium and osmolyte uptake membrane protein systems. Cyclic di‐AMP also targets stand‐alone CBS domain proteins such as DarB in Bacillus subtilis and CbpB in Listeria monocytogenes. We show here that the CbpB protein of Group B Streptococcus binds c‐di‐AMP with a very high affinity. Crystal structures of CbpB reveal the determinants of binding specificity and significant conformational changes occurring upon c‐di‐AMP binding. Deletion of the cbpB gene alters bacterial growth in low potassium conditions most likely due to a decrease in the amount of ppGpp caused by a loss of interaction between CbpB and Rel, the GTP/GDP pyrophosphokinase.

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Section: The C-di-amp Binding Sitesupporting

confidence: 76%

The c‐di‐AMP‐binding protein CbpB modulates the level of ppGpp alarmone in Streptococcus agalactiae

et al. 2023

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“…For example, OapA most closely approximates a CNNM protein without the CBS domains, which inspires our hypothesis that OLE RNAs might perform roles like those served by these missing protein domains. For example, various CBS domains are known to bind ligands with adenosyl moieties (Baykov et al, 2001; Scott et al, 2004), such as ATP (Li et al, 2015; Tseng et al, 2011) or c‐di‐AMP (Heidemann et al, 2022; Huynh et al, 2016; Schuster et al, 2016), sometimes to regulate the function of adjoining domains. An intriguing possibility is that OLE RNA functions as a c‐di‐AMP synthase to manipulate diverse processes (including stress responses) known to be regulated by this nucleotide‐derived signaling molecule (Fahmi et al, 2017; Stülke & Krüger, 2020; Zarrella & Bai, 2021).…”

Section: Speculation On the Function Of Ole Rnamentioning

confidence: 99%

Section: S Pecul Ati On On the Fun C Ti On Of Ole Rnamentioning

confidence: 99%

Evidence that OLE RNA is a component of a major stress‐responsive ribonucleoprotein particle in extremophilic bacteria

Breaker

Harris

Lyon

et al. 2023

Molecular Microbiology

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OLE RNA is a ~600‐nucleotide noncoding RNA present in many Gram‐positive bacteria that thrive mostly in extreme environments, including elevated temperature, salt, and pH conditions. The precise biochemical functions of this highly conserved RNA remain unknown, but it forms a ribonucleoprotein (RNP) complex that localizes to cell membranes. Genetic disruption of the RNA or its essential protein partners causes reduced cell growth under various stress conditions. These phenotypes include sensitivity to short‐chain alcohols, cold intolerance, reduced growth on sub‐optimal carbon sources, and intolerance of even modest concentrations of Mg2+. Thus, many bacterial species appear to employ OLE RNA as a component of an intricate RNP apparatus to monitor fundamental cellular processes and make physiological and metabolic adaptations. Herein we hypothesize that the OLE RNP complex is functionally equivalent to the eukaryotic TOR complexes, which integrate signals from various diverse pathways to coordinate processes central to cell growth, replication, and survival.

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“…CbpB (named DarB in B. subtilis ) is a stand‐alone CBS domain protein that directly interacts with the (p)ppGpp synthase RelA. The interaction enhances (p)ppGpp synthase activity, while c‐di‐AMP inhibits the activation by binding CbpB and dissociate the protein–protein interaction (Ainelo et al., 2023; Heidemann et al., 2022; Kruger et al., 2021; Peterson et al., 2020). In S. agalactiae , BusR and CbpB were further characterized (Covaleda‐Cortes et al., 2023; Devaux et al., 2018).…”

Section: C‐di‐amp‐binding Proteins In Streptococcimentioning

confidence: 99%

Bacterial second messenger cyclic di‐AMP in streptococci

Wright,

Bai

2023

Molecular Microbiology

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Cyclic dimeric adenosine monophosphate (c‐di‐AMP) has been well studied in bacteria, including those of the genus Streptococcus, since the first recognition of this dinucleotide in 2008. Streptococci possess a sole diadenylate cyclase, CdaA, and distinct c‐di‐AMP phosphodiesterases. Interestingly, cdaA is required for viability of some streptococcal species but not all when streptococci are grown in standard laboratory media. Bacteria of this genus also have distinct c‐di‐AMP effector proteins, diverse c‐di‐AMP‐signaling pathways, and subsequent biological outcomes. In streptococci, c‐di‐AMP may influence bacterial growth, morphology, biofilm formation, competence program, drug resistance, and bacterial pathogenesis. c‐di‐AMP secreted by streptococci has also been shown to interact with the mammalian host and induces immune responses including type I interferon production. In this review, we summarize the reported c‐di‐AMP networks in seven species of the genus Streptococcus, which cause diverse clinical manifestations, and propose future perspectives to investigate the signaling molecule in these streptococcal pathogens.

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Structural basis for c-di-AMP–dependent regulation of the bacterial stringent response by receptor protein DarB

Cited by 12 publications

References 53 publications

The c‐di‐AMP‐binding protein CbpB modulates the level of ppGpp alarmone in Streptococcus agalactiae

The c‐di‐AMP‐binding protein CbpB modulates the level of ppGpp alarmone in Streptococcus agalactiae

Evidence that OLE RNA is a component of a major stress‐responsive ribonucleoprotein particle in extremophilic bacteria

Bacterial second messenger cyclic di‐AMP in streptococci

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