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Scientific article
Open access
English

Steps for Shigella Gatekeeper Protein MxiC Function in Hierarchical Type III Secretion Regulation

Published inThe Journal of biological chemistry, vol. 292, no. 5, p. 1705-1723
Publication date2017-02
Abstract

Type III secretion systems are complex nanomachines used for injection of proteins from Gram-negative bacteria into eukaryotic cells. Although they are assembled when the environmental conditions are appropriate, they only start secreting upon contact with a host cell. Secretion is hierarchical. First, the pore-forming translocators are released. Second, effector proteins are injected. Hierarchy between these protein classes is mediated by a conserved gatekeeper protein, MxiC, in Shigella. As its molecular mechanism of action is still poorly understood, we used its structure to guide site-directed mutagenesis and to dissect its function. We identified mutants predominantly affecting all known features of MxiC regulation as follows: secretion of translocators, MxiC and/or effectors. Using molecular genetics, we then mapped at which point in the regulatory cascade the mutants were affected. Analysis of some of these mutants led us to a set of electron paramagnetic resonance experiments that provide evidence that MxiC interacts directly with IpaD. We suggest how this interaction regulates a switch in its conformation that is key to its functions.

eng
Keywords
  • Gram-negative bacteria
  • MxiC
  • Shigella
  • Biophysics
  • Cellular regulation
  • Electron paramagnetic resonance (EPR)
  • Molecular genetics
  • Protein secretion
  • Type III secretion system (T3SS)
Affiliation Not a UNIGE publication
Funding
  • University of Bristol - [Senior Research Fellowship]
  • Medical Research Council - [MR/J002097/1]
  • Freie Universität Berlin - [Research support]
  • Wellcome Trust - [WT088266]
Citation (ISO format)
ROEHRICH, A. Dorothea et al. Steps for <i>Shigella </i>Gatekeeper Protein MxiC Function in Hierarchical Type III Secretion Regulation. In: The Journal of biological chemistry, 2017, vol. 292, n° 5, p. 1705–1723. doi: 10.1074/jbc.M116.746826
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Article (Published version)
Identifiers
ISSN of the journal0021-9258
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