Publication
Title
A unique hetero-hexadecameric architecture displayed by the Escherichia coli O157 PaaA2-ParE2 antitoxin-toxin complex
Author
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 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. (C) 2016 Elsevier Ltd. All rights reserved.
Language
English
Source (journal)
Journal of molecular biology. - London
Publication
London : 2016
ISSN
0022-2836
Volume/pages
428:8(2016), p. 1589-1603
ISI
000375335800009
Full text (Publisher's DOI)
Full text (publisher's version - intranet only)
UAntwerpen
Project info
BIOSTRUCT-X: Transnational access and enhancement of integrated Biological Structure determination at synchrotron X-ray radiation facilities
Publication type
Subject
External links
Web of Science
Record
Identification
Creation 04.10.2018
Last edited 26.07.2021