SilE is an intrinsically disordered periplasmic “molecular sponge” involved in bacterial silver resistance

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.