Dissecting protein-protein interactions facilitating secretion of the virulence factor EspC by enteropathogenic Escherichia coli

This study investigates the domain structure and secretion of the autotransporter (AT) EspC, secreted by enteropathogenic Escherichia coli (EPEC). The boundaries of the archetypical signal peptide and beta-domain surrounding the passenger domain of EspC were established. Then, structural modelling w...

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Main Author: Bishop, Keith
Format: Thesis (University of Nottingham only)
Language:English
Published: 2009
Subjects:
Online Access:https://eprints.nottingham.ac.uk/11023/
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author Bishop, Keith
author_facet Bishop, Keith
author_sort Bishop, Keith
building Nottingham Research Data Repository
collection Online Access
description This study investigates the domain structure and secretion of the autotransporter (AT) EspC, secreted by enteropathogenic Escherichia coli (EPEC). The boundaries of the archetypical signal peptide and beta-domain surrounding the passenger domain of EspC were established. Then, structural modelling was used to define a region of EspC between the passenger- and β-domains, termed the inter-domain, which may comprise a passenger- chaperone domain. Yeast two-hybrid and co-purification approaches were subsequently used to assess protein-protein interactions between individual EspC domains and with a putative secretion accessory factor, YbgC. Direct interaction between the EspC passenger- and inter-domain was observed, consistent with a proposed chaperone function for the inter-domain. Structural modelling identified conserved surface motifs within the inter-region as targets for mutagenesis to determine their influence upon EspC secretion. Complementation of an EPEC espC mutant strain with inter-domain EspC mutants showed profound affects on secretion. Furthermore, these mutants had a dominant-negative affect on wildtype EspC secretion, affecting bacterial cell viability. These results provide the first characterisation of the putative EspC inter-domain and implicate it in facilitating efficient AT secretion. Observations from this work provide a foundation and rational direction for future research and a broad complement of research tools which will greatly facilitate future studies.
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format Thesis (University of Nottingham only)
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language English
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spelling nottingham-110232025-02-28T11:10:50Z https://eprints.nottingham.ac.uk/11023/ Dissecting protein-protein interactions facilitating secretion of the virulence factor EspC by enteropathogenic Escherichia coli Bishop, Keith This study investigates the domain structure and secretion of the autotransporter (AT) EspC, secreted by enteropathogenic Escherichia coli (EPEC). The boundaries of the archetypical signal peptide and beta-domain surrounding the passenger domain of EspC were established. Then, structural modelling was used to define a region of EspC between the passenger- and β-domains, termed the inter-domain, which may comprise a passenger- chaperone domain. Yeast two-hybrid and co-purification approaches were subsequently used to assess protein-protein interactions between individual EspC domains and with a putative secretion accessory factor, YbgC. Direct interaction between the EspC passenger- and inter-domain was observed, consistent with a proposed chaperone function for the inter-domain. Structural modelling identified conserved surface motifs within the inter-region as targets for mutagenesis to determine their influence upon EspC secretion. Complementation of an EPEC espC mutant strain with inter-domain EspC mutants showed profound affects on secretion. Furthermore, these mutants had a dominant-negative affect on wildtype EspC secretion, affecting bacterial cell viability. These results provide the first characterisation of the putative EspC inter-domain and implicate it in facilitating efficient AT secretion. Observations from this work provide a foundation and rational direction for future research and a broad complement of research tools which will greatly facilitate future studies. 2009-10-15 Thesis (University of Nottingham only) NonPeerReviewed application/pdf en arr https://eprints.nottingham.ac.uk/11023/1/2009_06_17_KB_MPhil_Thesis.pdf Bishop, Keith (2009) Dissecting protein-protein interactions facilitating secretion of the virulence factor EspC by enteropathogenic Escherichia coli. MPhil thesis, University of Nottingham. EspC Y2H Yeast two-hybrid Enteropathogenic Escherichia coli EPEC
spellingShingle EspC
Y2H
Yeast two-hybrid
Enteropathogenic Escherichia coli
EPEC
Bishop, Keith
Dissecting protein-protein interactions facilitating secretion of the virulence factor EspC by enteropathogenic Escherichia coli
title Dissecting protein-protein interactions facilitating secretion of the virulence factor EspC by enteropathogenic Escherichia coli
title_full Dissecting protein-protein interactions facilitating secretion of the virulence factor EspC by enteropathogenic Escherichia coli
title_fullStr Dissecting protein-protein interactions facilitating secretion of the virulence factor EspC by enteropathogenic Escherichia coli
title_full_unstemmed Dissecting protein-protein interactions facilitating secretion of the virulence factor EspC by enteropathogenic Escherichia coli
title_short Dissecting protein-protein interactions facilitating secretion of the virulence factor EspC by enteropathogenic Escherichia coli
title_sort dissecting protein-protein interactions facilitating secretion of the virulence factor espc by enteropathogenic escherichia coli
topic EspC
Y2H
Yeast two-hybrid
Enteropathogenic Escherichia coli
EPEC
url https://eprints.nottingham.ac.uk/11023/