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
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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.
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- 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.
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Further reading
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- Structural Biology and Molecular Biophysics
