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    Allosteric signalling in the outer membrane translocation domain of PapC usher

    Farabella, Irene and Pham, T. and Henderson, N.S. and Geibel, Sebastien and Phan, Gilles and Thanassi, D.G. and Delcour, A.H. and Waksman, Gabriel and Topf, Maya (2014) Allosteric signalling in the outer membrane translocation domain of PapC usher. eLife 3 , ISSN 2050-084X.

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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.

    Metadata

    Item Type: Article
    School: Birkbeck Schools and Departments > School of Science > Biological Sciences
    Research Centre: Bioinformatics, Bloomsbury Centre for, Structural Molecular Biology, Institute of (ISMB)
    Depositing User: Administrator
    Date Deposited: 02 Oct 2014 10:21
    Last Modified: 07 Dec 2016 15:02
    URI: http://eprints.bbk.ac.uk/id/eprint/10640

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