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Journal Articles Physical Chemistry Chemical Physics Year : 2023

Structural and dynamical insights into SilE silver binding from combined analytical probes

Abstract

Silver has been used for its antimicrobial properties to fight infection for thousands of years. Unfortunately, some Gram-negative bacteria have developed silver resistance causing the death of patients in a burn unit. The genes responsible for silver resistance have been designated as the sil operon. Among the proteins of the sil operon, SilE has been shown to play a key role in bacterial silver resistance. Based on the limited information available, it has been depicted as an intrinsically disordered protein that folds into helices upon silver ion binding. Herein, this work demonstrates that SilE is composed of 4 clearly identified helical segments in the presence of several silver ions. The combination of analytical and biophysical techniques (NMR spectroscopy, CD, SAXS, HRMS, CE-ICP-MS, and IM-MS) reveals that SilE harbors four strong silver binding sites among the eight sites available. We have also further evidenced that SilE does not adopt a globular structure but rather samples a large conformational space from elongated to more compact structures. This particular structural organization facilitates silver binding through much higher accessibility of the involved His and Met residues. These valuable results will advance our current understanding of the role of SilE in the silver efflux pump complex mechanism and will help in the future rational design of inhibitors to fight bacterial silver resistance.
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Dates and versions

hal-03960103 , version 1 (16-02-2023)

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Yoan Monneau, Cyrielle Arrault, Coraline Duroux, Marie Martin, Fabien Chirot, et al.. Structural and dynamical insights into SilE silver binding from combined analytical probes. Physical Chemistry Chemical Physics, 2023, 25 (4), pp.3061-3071. ⟨10.1039/D2CP04206A⟩. ⟨hal-03960103⟩
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