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

作者：Sterckx Yann G J; Jove Thomas; Shkumatov Alexander V; Garcia Pino Abel; Geerts Lieselotte; De Kerpel Maia; Lah Jurij; De Greve Henri; Van Melderen Laurence; Loris Remy^*

来源：Journal of Molecular Biology, 2016, 428(8): 1589-1603.

DOI：10.1016/j.jmb.2016.03.007

• RelE/ParE toxin superfamily
• protein protein interaction
• molecular recognition
• protein structure

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 0157 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 alpha-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.

• 出版日期2016-4-24