Title | A unique hetero-hexadecameric architecture displayed by the Escherichia coli O157 PaaA2-ParE2 antitoxin-toxin complex. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Sterckx, Y. G. - J., T. Jové, A. V. Shkumatov, A. Garcia-Pino, L. Geerts, M. De Kerpel, J. Lah, H. De Greve, L. Van Melderen, and R. Loris |
Journal | J Mol Biol |
Volume | 428 |
Issue | 8 |
Pagination | 1589-603 |
Date Published | 2016 Apr 24 |
ISSN | 1089-8638 |
Keywords | Amino Acid Sequence, Antitoxins, Bacterial Toxins, Calorimetry, Chromatography, Gel, Crystallography, X-Ray, DNA Gyrase, Enterotoxins, Escherichia coli O157, Escherichia coli Proteins, Molecular Conformation, Molecular Sequence Data, Phylogeny, Protein Multimerization, Surface Plasmon Resonance |
Abstract | Many bacterial pathogens modulate their metabolic activity, virulence and pathogenicity through so-called "toxin-antitoxin" (TA) modules. The genome of the human pathogen Escherichia coli O157 contains two three-component TA modules related to the known parDE module. Here, we show that the toxin EcParE2 maps in a branch of the RelE/ParE toxin superfamily that is distinct from the branches that contain verified gyrase and ribosome inhibitors. The structure of EcParE2 closely resembles that of Caulobacter crescentus ParE but shows a distinct pattern of conserved surface residues, in agreement with its apparent inability to interact with GyrA. The antitoxin EcPaaA2 is characterized by two α-helices (H1 and H2) that serve as molecular recognition elements to wrap itself around EcParE2. Both EcPaaA2 H1 and H2 are required to sustain a high-affinity interaction with EcParE2 and for the inhibition of EcParE2-mediated killing in vivo. Furthermore, evidence demonstrates that EcPaaA2 H2, but not H1, determines specificity for EcParE2. The initially formed EcPaaA2-EcParE2 heterodimer then assembles into a hetero-hexadecamer, which is stable in solution and is formed in a highly cooperative manner. Together these findings provide novel data on quaternary structure, TA interactions and activity of a hitherto poorly characterized family of TA modules. |
DOI | 10.1016/j.jmb.2016.03.007 |
Alternate Journal | J. Mol. Biol. |
PubMed ID | 26996937 |
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