Erschienen in:
The FEBS Journal, 282 (2015) 2, Seite 203-214
Sprache:
Englisch
DOI:
10.1111/febs.13129
ISSN:
1742-464X;
1742-4658
Entstehung:
Anmerkungen:
Beschreibung:
The growing emergence of antibiotic‐resistant bacteria has led to the exploration of naturally occurring defense peptides as antimicrobials. In this study, we found that laterosporulin (LS), a class IId bacteriocin, effectively kills active and nonmultiplying cells of both Gram‐positive and Gram‐negative bacteria. Fluorescence and electron microscopy suggest that growth inhibition occurs because of increased membrane permeability. The crystal structure of LS at 2.0 Å resolution reveals an all‐β conformation of this peptide, with four β‐strands forming a twisted β‐sheet. All six intrinsic cysteines are intramolecularly disulfide‐bonded, with two disulfides constraining the N terminus of the peptide and the third disulfide crosslinking the extreme C terminus, resulting in the formation of a closed structure. The significance of disulfides in maintaining the in‐solution peptide structure was confirmed by CD and fluorescence analyses. Despite a low overall sequence similarity, LS has disulfide connectivity [CI–CV, CII–CIV, and CIII–CVI] like that of β‐defensins and a striking architectural similarity with α‐defensins. Therefore LS presents a missing link between bacteriocins and mammalian defensins, and is also a potential antimicrobial lead, in particular against nonmultiplying bacteria.DatabaseThe atomic coordinates and the structure factors have been deposited in the Protein Data Bank under accession number 4OZK