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Backbone Interactions Between Transcriptional Activator ExsA and Anti-Activator ExsD Facilitate Regulation of the Type III Secretion System in Pseudomonas aeruginosa
by
Bernhards, Robert C.
, Schubot, Florian D.
, Fu, Yichen
, Shrestha, Manisha
, Ryan, Kylie
in
631/326
/ 631/337
/ Bacteria
/ Bacterial Proteins - chemistry
/ Bacterial Proteins - genetics
/ Bacterial Proteins - metabolism
/ Binding Sites
/ Cytoplasm
/ Cytotoxicity
/ Gene expression
/ Gram-negative bacteria
/ Humanities and Social Sciences
/ Kinases
/ multidisciplinary
/ Mutagenesis, Site-Directed
/ Protein Interaction Domains and Motifs
/ Protein Structure, Tertiary
/ Proteins
/ Pseudomonas aeruginosa
/ Pseudomonas aeruginosa - metabolism
/ Pseudomonas aeruginosa - pathogenicity
/ Repressor Proteins - chemistry
/ Repressor Proteins - genetics
/ Repressor Proteins - metabolism
/ Science
/ Science (multidisciplinary)
/ Secretion
/ Site-directed mutagenesis
/ Trans-Activators - chemistry
/ Trans-Activators - genetics
/ Trans-Activators - metabolism
/ Transcription, Genetic
/ Type III Secretion Systems - genetics
/ Type III Secretion Systems - metabolism
/ Virulence
2020
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Backbone Interactions Between Transcriptional Activator ExsA and Anti-Activator ExsD Facilitate Regulation of the Type III Secretion System in Pseudomonas aeruginosa
by
Bernhards, Robert C.
, Schubot, Florian D.
, Fu, Yichen
, Shrestha, Manisha
, Ryan, Kylie
in
631/326
/ 631/337
/ Bacteria
/ Bacterial Proteins - chemistry
/ Bacterial Proteins - genetics
/ Bacterial Proteins - metabolism
/ Binding Sites
/ Cytoplasm
/ Cytotoxicity
/ Gene expression
/ Gram-negative bacteria
/ Humanities and Social Sciences
/ Kinases
/ multidisciplinary
/ Mutagenesis, Site-Directed
/ Protein Interaction Domains and Motifs
/ Protein Structure, Tertiary
/ Proteins
/ Pseudomonas aeruginosa
/ Pseudomonas aeruginosa - metabolism
/ Pseudomonas aeruginosa - pathogenicity
/ Repressor Proteins - chemistry
/ Repressor Proteins - genetics
/ Repressor Proteins - metabolism
/ Science
/ Science (multidisciplinary)
/ Secretion
/ Site-directed mutagenesis
/ Trans-Activators - chemistry
/ Trans-Activators - genetics
/ Trans-Activators - metabolism
/ Transcription, Genetic
/ Type III Secretion Systems - genetics
/ Type III Secretion Systems - metabolism
/ Virulence
2020
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Backbone Interactions Between Transcriptional Activator ExsA and Anti-Activator ExsD Facilitate Regulation of the Type III Secretion System in Pseudomonas aeruginosa
by
Bernhards, Robert C.
, Schubot, Florian D.
, Fu, Yichen
, Shrestha, Manisha
, Ryan, Kylie
in
631/326
/ 631/337
/ Bacteria
/ Bacterial Proteins - chemistry
/ Bacterial Proteins - genetics
/ Bacterial Proteins - metabolism
/ Binding Sites
/ Cytoplasm
/ Cytotoxicity
/ Gene expression
/ Gram-negative bacteria
/ Humanities and Social Sciences
/ Kinases
/ multidisciplinary
/ Mutagenesis, Site-Directed
/ Protein Interaction Domains and Motifs
/ Protein Structure, Tertiary
/ Proteins
/ Pseudomonas aeruginosa
/ Pseudomonas aeruginosa - metabolism
/ Pseudomonas aeruginosa - pathogenicity
/ Repressor Proteins - chemistry
/ Repressor Proteins - genetics
/ Repressor Proteins - metabolism
/ Science
/ Science (multidisciplinary)
/ Secretion
/ Site-directed mutagenesis
/ Trans-Activators - chemistry
/ Trans-Activators - genetics
/ Trans-Activators - metabolism
/ Transcription, Genetic
/ Type III Secretion Systems - genetics
/ Type III Secretion Systems - metabolism
/ Virulence
2020
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Backbone Interactions Between Transcriptional Activator ExsA and Anti-Activator ExsD Facilitate Regulation of the Type III Secretion System in Pseudomonas aeruginosa
Journal Article
Backbone Interactions Between Transcriptional Activator ExsA and Anti-Activator ExsD Facilitate Regulation of the Type III Secretion System in Pseudomonas aeruginosa
2020
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Overview
The type III secretion system (T3SS) is a pivotal virulence mechanism of many Gram-negative bacteria. During infection, the syringe-like T3SS injects cytotoxic proteins directly into the eukaryotic host cell cytoplasm. In
Pseudomonas aeruginosa
, expression of the T3SS is regulated by a signaling cascade involving the proteins ExsA, ExsC, ExsD, and ExsE. The AraC-type transcription factor ExsA activates transcription of all T3SS-associated genes. Prior to host cell contact, ExsA is inhibited through direct binding of the anti-activator protein ExsD. Host cell contact triggers secretion of ExsE and sequestration of ExsD by ExsC to cause the release of ExsA. ExsA does not bind ExsD through the canonical ligand binding pocket of AraC-type proteins. Using site-directed mutagenesis and a specific
in vitro
transcription assay, we have now discovered that backbone interactions between the amino terminus of ExsD and the ExsA beta barrel constitute a pivotal part of the ExsD-ExsA interface. Follow-up bacterial two-hybrid experiments suggest additional contacts create an even larger protein–protein interface. The discovered role of the amino terminus of ExsD in ExsA binding explains how ExsC might relieve the ExsD-mediated inhibition of T3SS gene expression, because the same region of ExsD interacts with ExsC following host cell contact.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 631/337
/ Bacteria
/ Bacterial Proteins - chemistry
/ Bacterial Proteins - genetics
/ Bacterial Proteins - metabolism
/ Humanities and Social Sciences
/ Kinases
/ Protein Interaction Domains and Motifs
/ Proteins
/ Pseudomonas aeruginosa - metabolism
/ Pseudomonas aeruginosa - pathogenicity
/ Repressor Proteins - chemistry
/ Repressor Proteins - genetics
/ Repressor Proteins - metabolism
/ Science
/ Trans-Activators - chemistry
/ Trans-Activators - metabolism
/ Type III Secretion Systems - genetics
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