The intramolecular disulfide‐stapled structure of laterosporulin, a class IId bacteriocin, conceals a human defensin‐like structural module. (20th November 2014)

• Record Type: Journal Article
• Authors: Singh, Pradip Kumar; Solanki, Vipul; Sharma, Shalley; Thakur, Krishan Gopal; Krishnan, Beena; Korpole, Suresh
• Is Part Of: FEBS journal. Volume 282:Number 2(2015)
• Page Start: 203
• Page End: 214
• Publication Date: 2014-11-20
• Subjects: Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pathology, Molecular -- Periodicals; 572
• DOI: 10.1111/febs.13129
• Languages: English
• ISSNs: 1742-464X

Abstract

<abstract abstract-type="main" id="febs13102-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="febs13129-sec-0001" sec-type="section"> <p>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<sup>I</sup>–C<sup>V</sup>, C<sup>II</sup>–C<sup>IV</sup>, and C<sup>III</sup>–C<sup>VI</sup>] 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.</p> </sec> <sec id="febs13129-sec-0002" sec-type="section"> <title>Database</title> <p>The atomic coordinates and the structure factors have been deposited in the Protein Data Bank under accession number <ext-link ext-link-type="uri" xlink:href="http://www.rcsb.org/pdb/search/structidSearch.do?structureId=4OZK" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">4OZK</ext-link></p> </sec> </abstract>