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

Yann Georges Sterckx, Thomas Jove, Aliaksandr Shkumatau, Abel Garcia Pino, Lieselotte Geerts, Maia De Kerpel, Jurij Lah, Henri De Greve, Laurence Van Melderen, Remy Loris

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)


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.
Original languageEnglish
Pages (from-to)1589-1603
Number of pages14
JournalJ Mol Biol
Publication statusPublished - 2016


  • Structural Biology
  • Persistence
  • Toxin-antitoxin module
  • X-ray crystallography
  • SAXS
  • Molecular biophysics
  • Bacterial stress response


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