Peptide Structure and Silver Ion Affinity: Influence on the Formation of α-Helices upon Metal Binding

Abstract

Metal ion binding is essential for many critical life-sustaining protein functions. To clarify Ag + resistance, we studied model peptides based on the SilE protein. By focusing on a specific sequence of SilE known to form α-helices and mutants thereof, we discovered trends in the α-helical structure induced by Ag + .Silver, in its ionic or nanoparticle form, has been demonstrated to possess antimicrobial properties. [1][2][3] While the precise mechanisms underlying this phenomenon remain to be fully elucidated, research has shown that treating bacteria with silver results in the interference of silver ions with biomolecules, leading to their alteration. [4][5] These comprise alteration of the cell membrane, 6-7 condensation of DNA by intercalation into base pairs, 7-8 protein damages (e.g., mismetallation, liganding thiol groups (-SH), or iron-sulfur destabilization), [9][10][11] and direct or indirect production of reactive oxygen species (ROS) 7,8,10 . Consequently, these factors culminate in the inhibition of cell respiration, ultimately leading to the demise of the bacteria. [4][5] However, some Gram-negative bacteria, such as Salmonella Typhimurium, have developed a remarkable degree of tolerance to the antimicrobial effect of silver, which exceeds that observed in other bacterial strains. [12][13][14][15] This phenomenon can be attributed to the expression of a silver efflux pump, which is known as the Sil system (Fig. 1). 12 The system consists of eight proteins that work together to actively export Ag + out of the bacteria. In more detail, the periplasmic sensor SilS detects the arrival of Ag + and subsequently activates the response regulator SilR, which in turn induces the transcription of the SilPFABC operon. 12 Among these components, it has been suggested that SilP functions as a P-type ATPase. 17 This type of pump is known