The intramolecular disulfide-stapled structure of laterosporulin, a class IId bacteriocin, conceals a human defensin-like structural module.

Singh, Pradip Kumar and Solanki, Vipul and Sharma, Shalley and Thakur, Krishan Gopal and Krishnan, Beena and Korpole, Suresh (2015) The intramolecular disulfide-stapled structure of laterosporulin, a class IId bacteriocin, conceals a human defensin-like structural module. The FEBS journal, 282 (2). pp. 203-14. ISSN 1742-4658

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Abstract

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 [C(I)-C(V), C(II)-C(IV), and C(III)-C(VI)] 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.

Item Type:	Article
Additional Information:	Copyright of this article belongs to Oxford University Press.
Uncontrolled Keywords:	X-ray crystallography; bacteriocin; defensin; microscopy; nonmultiplying cells
Subjects:	Q Science > QR Microbiology
Depositing User:	Dr. K.P.S.Sengar
Date Deposited:	13 Jul 2015 10:41
Last Modified:	14 Jul 2015 05:12
URI:	http://crdd.osdd.net/open/id/eprint/1651

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