Allosteric signalling in the outer membrane translocation domain of PapC usher
- Birkbeck College, United Kingdom
- University of Houston, United States
- Stony Brook University, United States
- University of Würzburg, Germany
- Université Paris Descartes, France
- Cited 13
- Views 1,590
- Annotations
Abstract
PapC ushers are outer-membrane proteins enabling assembly and secretion of P pili in uropathogenic E. coli. Their translocation domain is a large β-barrel occluded by a plug domain, which is displaced to allow the translocation of pilus subunits across the membrane. Previous studies suggested that this gating mechanism is controlled by a β-hairpin and an α-helix. To investigate the role of these elements in allosteric signal communication we developed a method combining evolutionary and molecular dynamics studies of the native translocation domain and mutants lacking the β-hairpin and/or α-helix. Analysis of a hybrid residue interaction network suggests distinct regions (residue 'communities') within the translocation domain (especially around β12-β14) linking these elements, thereby modulating PapC gating. Antibiotic sensitivity and electrophysiology experiments on a set of alanine-substitution mutants confirmed functional roles for four of these communities. This study illuminates the gating mechanism of PapC ushers and its importance in maintaining outer-membrane permeability.
Article and author information
Author details
Reviewing Editor
- Volker Dötsch, Goethe University, Germany
Publication history
- Received: May 30, 2014
- Accepted: September 29, 2014
- Accepted Manuscript published: October 1, 2014 (version 1)
- Version of Record published: October 28, 2014 (version 2)
- Version of Record updated: September 27, 2016 (version 3)
Copyright
© 2014, Farabella et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 1,590
- Page views
-
- 106
- Downloads
-
- 13
- Citations
Article citation count generated by polling the highest count across the following sources: Crossref, Scopus, PubMed Central.
Download links
Downloads (link to download the article as PDF)
Download citations (links to download the citations from this article in formats compatible with various reference manager tools)
Open citations (links to open the citations from this article in various online reference manager services)
Further reading
-
- Structural Biology and Molecular Biophysics
