A unique hetero-hexadecameric architecture displayed by the Escherichia coli O157 PaaA2–ParE2 antitoxin–toxin complex

Sterckx, Yann G.J.; Jové, Thomas; Shkumatov, Alexander V.; García-Pino, Abel; Geerts, Lieselotte; Kerpel, Maia De; Lah, Jurij; Greve, Henri De; Melderen, Laurence Van; Loris, Remy

doi:10.1016/j.jmb.2016.03.007

Cited by 34 publications

(51 citation statements)

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“…Notable differences are observed for the packing of the C-terminal helix against the β-sheet core and for loop β2-β3, which is structured and significantly shorter in Ec RelE (Figure 1B). Apart from Ec RelE, Vc HigB2 shares high structural similarity with RelJ, YoeB, YafQ, the archeal RelEs (which are all ribonucleases,(15,19,46) and also with Caulobacter crescentus ParE and E. coli O157 ParE2 (48,49), which have different biochemical activities (Supplementary Figure S2, sequence identities and DALI scores are given in Supplementary Table S2). Surprisingly, plasmid-born Pv HigB, together with BrnT from Brucella abortus and MqsR from E. coli belongs to the more distant relatives (Supplementary Figure S2 and Table S2, (17,18)).…”

Section: Resultsmentioning

confidence: 99%

Ribosome-dependent Vibrio cholerae mRNAse HigB2 is regulated by a β-strand sliding mechanism

Hadži

García-Pino

Haesaerts

et al. 2017

Nucleic Acids Research

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Toxin–antitoxin (TA) modules are small operons involved in bacterial stress response and persistence. higBA operons form a family of TA modules with an inverted gene organization and a toxin belonging to the RelE/ParE superfamily. Here, we present the crystal structures of chromosomally encoded Vibrio cholerae antitoxin (VcHigA2), toxin (VcHigB2) and their complex, which show significant differences in structure and mechanisms of function compared to the higBA module from plasmid Rts1, the defining member of the family. The VcHigB2 is more closely related to Escherichia coli RelE both in terms of overall structure and the organization of its active site. VcHigB2 is neutralized by VcHigA2, a modular protein with an N-terminal intrinsically disordered toxin-neutralizing segment followed by a C-terminal helix-turn-helix dimerization and DNA binding domain. VcHigA2 binds VcHigB2 with picomolar affinity, which is mainly a consequence of entropically favorable de-solvation of a large hydrophobic binding interface and enthalpically favorable folding of the N-terminal domain into an α-helix followed by a β-strand. This interaction displaces helix α3 of VcHigB2 and at the same time induces a one-residue shift in the register of β-strand β3, thereby flipping the catalytically important Arg64 out of the active site.

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Section: Resultsmentioning

confidence: 99%

Ribosome-dependent Vibrio cholerae mRNAse HigB2 is regulated by a β-strand sliding mechanism

Hadži

García-Pino

Haesaerts

et al. 2017

Nucleic Acids Research

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“…Bioinformatic searches and structural comparisons have detected the relationship between RelE-family toxins and those similar to ParE encoded by RK2 plasmid (Anantharaman and Aravind, 2003;Sterckx et al, 2016). ParE-family toxins act at the level of DNA replication by poisoning DNA-gyrase or by currently unidentified mechanisms (Jiang et al, 2002;Hallez et al, 2010;Yuan et al, 2010;Sterckx et al, 2016).…”

Section: Mrna Cleavage In the Ribosome By Rele Toxinsmentioning

confidence: 99%

The Variety in the Common Theme of Translation Inhibition by Type II Toxin–Antitoxin Systems

Jurėnas

Melderen

2020

Front. Genet.

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Type II Toxin-antitoxin (TA) modules are bacterial operons that encode a toxic protein and its antidote, which form a self-regulating genetic system. Antitoxins put a halter on toxins in many ways that distinguish different types of TA modules. In type II TA modules, toxin and antitoxin are proteins that form a complex which physically sequesters the toxin, thereby preventing its toxic activity. Type II toxins inhibit various cellular processes, however, the translation process appears to be their favorite target and nearly every step of this complex process is inhibited by type II toxins. The structural features, enzymatic activities and target specificities of the different toxin families are discussed. Finally, this review emphasizes that the structural folds presented by these toxins are not restricted to type II TA toxins or to one particular cellular target, and discusses why so many of them evolved to target translation as well as the recent developments regarding the role(s) of these systems in bacterial physiology and evolution.

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“…(A) ParE2-like toxin; (B) PaaA2-like antitoxin. The imperfect superimposition on the backbone trace of the PaaA2 antitoxin (B) is probably due to the intrinsically disordered structure of the toxin-binding domain, which provides a certain degree of overall flexibility needed for the interaction with the toxin, a feature in common with several type II antitoxins (23). Only the first-ranked model predicted by I-TASSER (47) for each query is shown.…”

Section: Figmentioning

confidence: 99%

New Shuttle Vectors for Gene Cloning and Expression in Multidrug-Resistant Acinetobacter Species

Lucidi

Runci

Rampioni

et al. 2018

Antimicrob Agents Chemother

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Understanding bacterial pathogenesis requires adequate genetic tools to assess the role of individual virulence determinants by mutagenesis and complementation assays, as well as for homologous and heterologous expression of cloned genes. Our knowledge of pathogenesis has so far been limited by the scarcity of genetic tools to manipulate multidrug-resistant (MDR) epidemic strains, which are responsible for most infections. Here, we report on the construction of new multipurpose shuttle plasmids, namely, pVRL1 and pVRL2, which can efficiently replicate in spp. and in The pVRL1 plasmid has been constructed by combining (i) the cryptic plasmid pWH1277 from, which provides an origin of replication for spp.; (ii) a ColE1-like origin of replication; (iii) the gentamicin or zeocin resistance cassette for antibiotic selection; and (iv) a multilinker containing several unique restriction sites. Modification of pVRL1 led to the generation of the pVRL2 plasmid, which allows arabinose-inducible gene transcription with an undetectable basal expression level of cloned genes under uninduced conditions and a high dynamic range of responsiveness to the inducer. Both pVRL1 and pVRL2 can easily be selected in MDR, have a narrow host range and a high copy number, are stably maintained in spp., and appear to be compatible with indigenous plasmids carried by epidemic strains. Plasmid maintenance is guaranteed by the presence of a toxin-antitoxin system, providing more insights into the mechanism of plasmid stability in spp.

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A unique hetero-hexadecameric architecture displayed by the Escherichia coli O157 PaaA2–ParE2 antitoxin–toxin complex

Cited by 34 publications

References 68 publications

Ribosome-dependent Vibrio cholerae mRNAse HigB2 is regulated by a β-strand sliding mechanism

Ribosome-dependent Vibrio cholerae mRNAse HigB2 is regulated by a β-strand sliding mechanism

The Variety in the Common Theme of Translation Inhibition by Type II Toxin–Antitoxin Systems

New Shuttle Vectors for Gene Cloning and Expression in Multidrug-Resistant Acinetobacter Species

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