Intra-molecular Disulfide-Stapled Structure of Laterosporulin, a Class IId Bacteriocin, Conceals Human Defensin-like Structural Module. Singh PK, Solanki V, Sharma S, Thakur KG, Krishnan B, Korpole S., FEBS J., 2014, Oct 27. [Epub ahead of print]
The growing emergence of antibiotic-resistant bacteria has led to exploring naturally occurring defense peptides as antimicrobials. In this study, we report that laterosporulin, a class IId bacteriocin, effectively kills active and non-multiplying cells of both Gram-positive and Gram-negative bacteria. Fluorescence and electron microscopy suggest that growth inhibition occurs due to increased membrane permeability. Crystal structure of laterosporulin at 2.0 Ã… resolution reveals an all-Î² conformation of this peptide with four beta strands forming a twisted Î²-sheet. All the six intrinsic cysteine residues are intramolecularly disulfide bonded with two disulfides constraining the N-terminus of the peptide and the third disulfide crosslinks the extreme C-terminus resulting in the formation of a closed structure. Significance of disulfides in maintaining the in-solution peptide structure was confirmed by the circular dichroism and fluorescence analyses. Despite a low overall sequence similarity, laterosporulin has the disulfide connectivity [CI -CV , CII -CIV , CIII -CVI ] like Î²-defensins and a striking architectural similarity with Î±-defensins. Therefore laterosporulin presents a missing link between bacteriocins and mammalian defensins and is also a potential antimicrobial lead, in particular against non-multiplying bacteria. This article is protected by copyright. All rights reserved.