title: SilE is an intrinsically disordered periplasmic "molecular sponge" involved in bacterial silver resistance.
abstract: Ag(+) resistance was initially found on the Salmonella enetrica serovar Typhimurium multi-resistance plasmid pMG101 from burns patients in 1975. The putative model of Ag(+) resistance, encoded by the sil operon from pMG101, involves export of Ag(+) via an ATPase (SilP), an effluxer complex (SilCFBA) and a periplasmic chaperon of Ag(+) (SilE). SilE is predicted to be intrinsically disordered. We tested this hypothesis using structural and biophysical studies and show that SilE is an intrinsically disordered protein in its free apo-form but folds to a compact structure upon optimal binding to six Ag(+) ions in its holo-form. Sequence analyses and site-directed mutagenesis established the importance of histidine and methionine containing motifs for Ag(+) -binding, and identified a nucleation core that initiates Ag(+) -mediated folding of SilE. We conclude that SilE is a molecular sponge for absorbing metal ions.
authors.affiliation: School of Biosciences, University of Nottingham, Sutton, Bonington, LE12 5RD, United Kingdom.
authors.forename: Karishma R
authors.initials: KR
authors.lastname: Asiani
authors.affiliation: Centre for Biomolecular Sciences, School of Chemistry, University Park, University of Nottingham, Nottingham, NG7 2RD, United Kingdom.
authors.forename: Huw
authors.initials: H
authors.lastname: Williams
authors.affiliation: Oxford Protein Production Factory, Research Complex at Harwell, Rutherford Appleton Laboratory, Oxfordshire, OX11 0FA, United Kingdom.
authors.forename: Louise
authors.initials: L
authors.lastname: Bird
authors.affiliation: Department of Chemistry, University of Warwick, Gibbet Hill, Coventry, CV4 7AL, United Kingdom.
authors.forename: Matthew
authors.initials: M
authors.lastname: Jenner
authors.affiliation: Centre for Biomolecular Sciences, School of Chemistry, University Park, University of Nottingham, Nottingham, NG7 2RD, United Kingdom.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Searle
authors.affiliation: School of Biosciences, University of Nottingham, Sutton, Bonington, LE12 5RD, United Kingdom.
authors.forename: Jon L
authors.initials: JL
authors.lastname: Hobman
authors.affiliation: School of Biosciences, University of Nottingham, Sutton, Bonington, LE12 5RD, United Kingdom.|ISIS Neutron and Muon Source and Research Complex at Harwell, Rutherford Appleton Laboratory, Oxfordshire, OX11 0FA, United Kingdom.
authors.forename: David J
authors.initials: DJ
authors.lastname: Scott
authors.affiliation: Centre for Biomolecular Sciences, School of Chemistry, University Park, University of Nottingham, Nottingham, NG7 2RD, United Kingdom.
authors.forename: Panos
authors.initials: P
authors.lastname: Soultanas
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D024881:Drug Resistance, Bacterial; D004926:Escherichia coli / Q000235:genetics; D005798:Genes, Bacterial; D016297:Mutagenesis, Site-Directed; D009876:Operon; D019897:Periplasm / Q000378:metabolism; D010957:Plasmids / Q000187:drug effects / Q000378:metabolism; D012480:Salmonella Infections / Q000188:drug therapy / Q000382:microbiology; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D012834:Silver / Q000494:pharmacology*
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; C117203:SilE protein, Salmonella typhimurium; D012834:Silver; D000251:Adenosine Triphosphatases